# paper.pdf ## Metadata - PDFFormatVersion=1.7 - Language=en - IsLinearized=true - IsAcroFormPresent=false - IsXFAPresent=false - IsCollectionPresent=false - IsSignaturesPresent=false - Author=VA/DOD;Sigma Health Consulting - CreationDate=D:20251104082248-05'00' - Creator=Microsoft® Word for Microsoft 365 - ModDate=D:20251105154814-05'00' - Producer=Microsoft® Word for Microsoft 365 - Title=VA/DOD Clinical Practice Guideline for Management of Overweight and Obesity in Adults - pdf:producer=Microsoft® Word for Microsoft 365 - dc:format=application/pdf - dc:creator=VA/DOD;Sigma Health Consulting - dc:title=VA/DOD Clinical Practice Guideline for Management of Overweight and Obesity in Adults - xmp:creatortool=Microsoft® Word for Microsoft 365 - xmp:createdate=2025-11-04T08:22:48-05:00 - xmp:modifydate=2025-11-05T15:48:14-05:00 - xmp:metadatadate=2025-11-05T15:48:14-05:00 - xmpmm:documentid=uuid:4C29797A-9EF2-4FE9-988F-77971B39021C - xmpmm:instanceid=uuid:867cc95b-46d7-4409-a2c9-aaf5df31c986 ## Contents ### Page 1 # VA/DOD CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF ADULT OVERWEIGHT AND OBESITY Department of Veterans Affairs Department of Defense QUALIFYING STATEMENTS The Department of Veterans Affairs (VA) and the Department of Defense (DOD) guidelines are based on the best information available at the time of publication. The guidelines are designed to provide information and assist decision making. They are not intended to define a standard of care and should not be construed as one. Neither should they be interpreted as prescribing an exclusive course of management. This clinical practice guideline (CPG) is based on a systematic review of both clinical and epidemiological evidence. Developed by a panel of multidisciplinary experts, it provides a clear explanation of the logical relationships between various care options and health outcomes while rating both the quality of the evidence and the strength of the recommendation. Variations in practice will inevitably and appropriately occur when providers consider the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Therefore, every health care professional using these guidelines is responsible for evaluating the appropriateness of applying them in the setting of any clinical situation with a patient-centered approach. These guidelines are not intended to represent VA or DOD policies. Further, the inclusion of recommendations for specific testing, therapeutic interventions, or both within these guidelines does not guarantee coverage of civilian sector care. Version 4.0 – 2025 ### Page 2 Prepared by The Management of Overweight and Obesity in Adults Work Group With support from Office of Quality and Patient Safety, Veterans Health Administration And Clinical Quality Improvement Program, Defense Health Agency Version 4.0 – 20251 1 VA/DOD Clinical Practice Guideline. (2025). Management of Overweight and Obesity in Adults Work Group. Washington, DC: U.S. Government Printing Office. Based on evidence reviewed through January 2025 ### Page 3 ### Page 4 ### Page 5 ### Page 6 # I. Introduction The Department of Veterans Affairs (VA) and Department of Defense (DOD) Evidence Based Practice Work Group (EBPWG) was established and first chartered in 2004. Its mission is toadvise the “…Health Executive Council on the use of clinical and epidemiological evidence toimprove the health of the population across the Veterans Health Administration and MilitaryHealth System,” by facilitating the development of clinical practice guidelines (CPGs) for the VA and DOD populations.(4) The development and update of VA/DOD CPGs is funded by VAEvidence Based Practice, Office of Quality and Patient Safety. The system-wide goal of evidence-based CPGs is to improve patient health and well-being. In 2020, the VA and DOD updated the 2014 CPG for the Management of Adult Overweight and Obesity (2020 OBE CPG), based on evidence reviewed from February 1, 2013, to April 8, 2019. Since the release of the 2020 OBE CPG, the evidence base has expanded. Consequently, an update was recommended in 2024. This updated CPG uses the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, reflecting a rigorous application of the methodology.(5) Therefore, the strength of some recommendations may have beenmodified based on the confidence in the quality of the supporting evidence (seeEvidence Qualityand Recommendation Strength). The updated 2025 VA/DOD CPG for the Management of Overweight and Obesity in Adults includes objective, evidence-based information on managing overweight and obesity. Successful implementation of this CPG will assist providers in: - • Assessing the patient’s condition and, in collaboration with the patient, determining the most appropriate therapeutic plan; - • Optimizing each patient’s functional independence, health outcomes, and quality of life. - • Minimizing preventable complications and morbidity; and - • Emphasizing the use of patient-centered care. # II. Background ## A. Epidemiology, Physiology, and Impact in the General Population Overweight and obesity affect approximately 75% of U.S. adults.(6) Obesity alone affects 40% ofU.S. adults and is projected to rise to 50% by 2030.(7) Obesity is a chronic, relapsing,multifactorial, neurobehavioral disease. It is characterized by an excessive increase and storage of body fat, which leads to adverse metabolic, biomechanical, and psychosocial health consequences.(8,9) Obesity is also characterized by brain and hormonal dysfunctions that impairmetabolism and increase appetite, leading to abnormal weight gain and regain after weight loss, often despite efforts to apply and maintain lifestyle modifications.(10) Effective treatment requiresan individualized and comprehensive approach, including lifestyle interventions, obesity medications, and/or endoscopic and surgical bariatric procedures. Recognizing obesity as a disease is crucial for de-stigmatization and effective management, as it is associated with serious ### Page 7 health consequences, including cardiovascular diseases, diabetes, musculoskeletal disorders, and cancer, among others.(11) Obesity is defined as a chronic, relapsing, multifactorial disease characterized by abnormal or excessive adipose tissue accumulation that impairs health and increases the risk of comorbidities and premature mortality. The causes of obesity are multifactorial and include genetic susceptibility, environmental and social determinants, behavioral patterns, and physiological dysregulation of multiple systems, including neuroendocrine signaling, metabolism, and inflammation. The imbalance between energy intake and energy expenditure leads to the accumulation of excessive adiposity.(12-15) Weight regulation is governed by complex neuroendocrine mechanisms and adaptive physiological responses. While caloric restriction and increased energy expenditure can initially produce weight loss, these efforts trigger compensatory hormonal changes: levels of the hunger- promoting hormone ghrelin rise, while satiety hormones such as leptin, peptide YY (PYY), cholecystokinin (CCK), and glucagon-like peptide-1 (GLP-1) decrease.(16) These hormonal shiftsincrease appetite and reduce feelings of fullness. At the same time, resting and total energy expenditure may decline disproportionately relative to the loss of body mass, a phenomenon known as adaptive thermogenesis or metabolic adaptation, but whether this disproportionate reduction in metabolism occurs or even hinders weight loss is controversial.(17) This alteredphysiological state promotes weight regain, making long-term weight loss maintenance particularly difficult. Together, these processes underscore the biological challenges in managing obesity. However, evidence shows that comprehensive lifestyle interventions (CLI) plus obesity pharmacotherapy and metabolic/bariatric surgery when indicated, can counteract these adaptive responses and support sustained weight reduction.(8) Individualized, comprehensive treatmentnot only improves the durability of weight loss but also yields meaningful improvements in cardiometabolic health, physical function, and quality of life.(18) The most used screening tool for overweight and obesity is the Body Mass Index (BMI), calculated as weight in kilograms divided by height in meters squared (kg/m2), because it is low- cost, easy to use, scalable, and convenient.(19) From a public health and epidemiological standpoint, BMI is linked to many health outcomes, including health costs, morbidity, and mortality. At the population level, BMI correlates with the risk of developing adiposity-related health conditions. However, despite BMI being the primary method for diagnosis and staging, it has limitations in differentiating between body fat, lean muscle mass, and body fat distribution, making it less accurate at the individual level for predicting health risk.(20) Therefore, BMI should be used as a screening tool, but not alone to diagnose obesity. Anthropometric measurements such as waist circumference (WC) and waist-to-hip ratio are commonly used surrogate markers of abdominal or visceral fat. Epidemiological evidence links these indices to increased cardiometabolic risk and higher body fat percentage. However, their performance can vary across different populations and sexes. Additionally, they cannot reliably distinguish visceral fat from subcutaneous fat on an individual level. Despite these limitations, these measurements are more accurate than BMI in identifying increased adiposity and ### Page 8 individuals at higher risk of obesity-related complications, especially when combined with BMI, making them useful tools for early intervention.(11,21) Other advanced body composition imaging modalities (e.g., bioelectrical impedance analysis [BIA], dual-energy x-ray absorptiometry scan [DXA], and magnetic resonance imaging [MRI]) are more specific in identifying visceral adiposity and cardiometabolic risk. However, while imaging technologies offer enhanced precision, they can increase cost, be more time-consuming, and be impractical in routine clinical settings or on the scale required for population health management.(22) Consequently, from a clinical standpoint, the integration of BMI and anthropometric measurements can help identify phenotypes that may have a higher risk of developing obesity or obesity-related complications. Obesity is linked to more than 200 chronic health conditions and is associated with reduced quality of life (QoL) and decreased lifespan and health span, particularly in Class 2 and Class 3 obesity (seeTable O-1).(23-26) The relationship between BMI and mortality follows a J-shaped orU-shaped curve, suggesting that mortality is highest at both extremes of BMI, with the lowest risk observed at a BMI between 22 – 24 kg/m2.(26,27) Earlier studies that suggested overweightconferred a survival advantage were confounded by factors such as smoking, preexisting illness, and limited follow-up duration.(24,26) Overweight and obesity are major risk factors for numerous conditions, including type 2 diabetes mellitus (T2DM), hypertension (HTN), dyslipidemia, metabolic syndrome, osteoarthritis, obstructive sleep apnea (OSA), depression, metabolic dysfunction-associated steatotic liver disease (MASLD), Alzheimer’s disease, and various cancers.(2,28-32) The pathophysiology ofobesity-related diseases includes two primary mechanisms: adiposopathy (dysfunctional fat tissue) and fat mass effects (mechanical burden). Adipose tissue is now recognized as a complex, highly active metabolic and endocrine organ, rather than just an energy storage site. It consists of adipocytes, connective tissue matrix, nerve tissue, stromovascular cells, and immune cells, all functioning as an integrated unit. Adipose tissue responds to signals from traditional hormone systems and the central nervous system while also secreting key endocrine factors such as leptin, adiponectin, TNF-α, IL-6, MCP-1, plasminogen activator inhibitor-1, and resistin, which regulate metabolism, inflammation, and cardiovascular function. Adiposopathy occurs when excess adipose tissue becomes dysfunctional, driving a chronic inflammatory state that promotes insulin resistance, dyslipidemia, and cardiovascular disease, especially via excess visceral fat. In parallel, the mechanical effects of increased fat mass further contribute to disease by exerting mechanical stress on organs and joints, leading to conditions such as osteoarthritis, lymphedema, obstructive sleep apnea, and gastroesophageal reflux disease. Together, these mechanisms highlight how obesity is not just a matter of excess weight but a complex, disease-promoting condition affecting multiple organ systems.(33,34) There are strong connections between excess weight and the development of many chronic medical conditions and cardiovascular risk factors. The Framingham Heart Study indicated a strong link between obesity and essential hypertension, attributing 78% of cases in men and 65% ### Page 9 in women to obesity.(35) The duration of obesity also plays a significant role in blood pressure. Astudy in Mauritius, a country in the Indian Ocean,(36) found that a one standard deviation (SD)increase in BMI over five years was associated with a 30% higher risk of hypertension compared to individuals with stable weight. Long-term impact is also evident, as young adults with obesity in the Johns Hopkins Precursors Study had a threefold higher risk of hypertension 46 years later, regardless of later lifestyle changes.(37) Large epidemiologic studies in the United Statesdemonstrate that the prevalence of type 2 diabetes increases with increasing obesity class: among adults with class 1 obesity (BMI 30.0–34.9 kg/m²), prevalence is approximately 18–20%, rising to about 43% in those with class 3 obesity (BMI ≥40 kg/m²).(38) Adults with obesity werefour times as likely to have T2DM, and the Centers for Disease Control and Prevention (CDC) estimates that 9 out of 10 people with diagnosed T2DM have overweight or obesity.(39)Cardiovascular disease (CVD) accounts for 67.5% of deaths globally, with more than one-third of these deaths in persons with overweight.(40) Dyslipidemia affects 60-70% of adults with obesity(41) and is a major contributor to mortality and disability-adjusted life years (DALY)(41). Thedevelopment or worsening of T2DM, HTN, and dyslipidemia is particularly hazardous due to their independent effects on risk for coronary artery disease and stroke. CVD is the leading cause of death among individuals with a high BMI and a major contributor to mortality and DALY.(13,41-43) Obesity is also a leading contributor to MASLD, the most common cause of chronic liver disease, and a growing indication for liver transplantation. Prevalence is projected to reach 41.4% by 2050, accompanied by dramatic increases in cirrhosis, liver cancer, and transplant need. (44,45) Arecent study analyzing trends in the United States found MASLD-related age-standardized mortality rates (ASMRs) increased from 0.25 to 1.27 per 100,000 persons between 2006 and 2023, and ASMRs will continue to rise, reaching 2.24 per 100,000 by 2040, disproportionately impacting older adults, non-Hispanic Whites, and Hispanic individuals.(46) Obesity is the second most preventable cause of cancer in smokers and the leading cause of cancer in nonsmokers.(3) The National Cancer Institute reports that overweight and obesity areassociated with at least 13 types of cancer, accounting for 4.7% of new cases in men and 9.6% of new cases in women.(2) Obesity can negatively impact cancer survivorship, including quality oflife, risk of recurrence, disease progression, overall prognosis, and the likelihood of developing second primary cancers. A meta-analysis of over 6.3 million participants found that obesity is associated with increased overall and cancer-specific mortality, particularly in breast, colon, and uterine cancers. However, patients with obesity and renal cell carcinoma, lung cancer, or melanoma had better survival rates, possibly due to factors like the poor health status of individuals with very low BMI or the association of weight loss with frailty and smoking. These findings suggest that obesity generally worsens cancer prognosis, though certain cancers may show improved survival in patients with obesity.(47) Observational studies suggest that intentionalweight loss is linked to a reduced risk of breast, endometrial, colon, and prostate cancers, likely due to decreases in hormone levels such as insulin, estrogens, and androgens, which are known to contribute to cancer risk.(48) Bariatric surgery, in particular, is associated with reduced cancerincidence and improved survival in individuals with obesity.(49) Individuals with obesity consistently report lower health-related quality of life (HRQoL) scores, particularly in physical domains such as mobility, pain, and ability to perform usual activities, compared to those with normal weight. Obesity is also associated with increased prevalence of chronic pain, fatigue, insomnia, and reduced physical and psychological working ability, ### Page 10 independent of comorbidities. The adverse effects on quality of life persist even after adjusting for obesity-related comorbidities such as diabetes, hypertension, and osteoarthritis, indicating that high BMI itself is an independent risk factor for reduced well-being.(50,51) Individuals withoverweight and obesity perceive or experience stigma and discrimination across multiple domains, including employment, healthcare, and media representation.(52) Beyond personalsuffering, obesity imposes substantial financial burdens. From 2001 to 2015, expenditures related to obesity rose by nearly 30% and continue to rise.(53) In 2019, adults with obesity andoverweight incurred $1,861 and $600 more in annual medical expenses, respectively, than those with a healthy weight. This figure rose to $3,097 for adults with severe obesity defined by a BMI greater than or equal to 35.(54) Obesity was estimated to cost $260 billion in annual health carespending and is projected to grow to more than $385 billion in 2024.(55) Indirect costs fromincreased absenteeism from work, reduced productivity while at work (presenteeism), and higher rates of disability have been estimated at over $250 billion per year.(56) ## B. Overweight and Obesity in the Department of Defense and the Department of Veterans Affairs Populations and its Impact Overweight and obesity may be a threat to national security. A recent report indicated that as of 2020, approximately 77% of young adults ages 17-24 were disqualified from military service. 36% were disqualified due to their weight, and of those, 11% were disqualified based on weight alone, and 25% were disqualified due to weight and another factor.(57) This problem will only get worseas 50% of U.S. adults are predicted to have obesity by 2030.(58) The active-duty military and Veteran population have been similarly affected by increases in obesity. In 2002, less than 8% of active-duty Service members had a BMI within the obesity range.(57) In 2022, this number increased to 21.6% with 68% classified as having overweight orobesity according to the DOD’s Health of the Force 2022 Report, which provides an evidence- based portrait of the health and well-being of U.S. Service Members.(59) This represents anincrease from 2018, when the prevalence of obesity was 17%. Rates of obesity vary across branches of the Armed Services, including 11% (Marines), 21% (Army), 23% (Air Force), and 27% (Navy). Prevalence of obesity was highest in males and the age category of 35–44 years (32.5%). Obesity in the U.S. military is driven by a combination of biological, environmental, and systemic factors. While the military generally screens BMI and physical readiness at accession, waivers may be granted, particularly when applicants meet performance benchmarks despite elevated BMI. Additionally, some services offer preparatory courses to help interested recruitsmeet weight standards. For example, the Army’s Future Soldier Preparatory Course permits prospective recruits who exceed the standard body fat percentage by up to 6%, based on age, sex, and height, to enroll in a structured 90-day program emphasizing physical training andnutritional guidance. Upon achieving a reduction to 2% above the Army’s body fat standards,participants are eligible to advance to basic training, with the expectation of continued weight loss during basic training.(60) This has resulted in a higher number of Service members who start theircareers already at risk for obesity-related conditions. Furthermore, the risk for weight regain following basic training is high due to high-stress environments, inconsistent sleep, poor dietary options, and decreased time for exercise. Obesity is complicated by genetic predispositions and neurobehavioral mechanisms that make sustained weight loss difficult. Despite these ### Page 11 complexities, military policies often frame obesity as a matter of discipline rather than health. Evidence dictates that obesity is a chronic disease requiring medical treatment and support.(61) Millennium Cohort Study data from 2001-2008 found a doubling of obesity rates per BMI in Service members (10-20%) with statistically significant increased rates of hypertension, type 2 diabetes, obstructive sleep apnea, depression, and post-traumatic stress disorder.(62) Severalanalyses reported that Service members with obesity were 33-47% more likely to suffer musculoskeletal injuries(63,64), contributing to more than 3.6 million injuries that occurred amongService members between 2008 and 2017.(65) The consequences of obesity in active-dutyService members may negatively influence a range of operations related to recruitment, retention, resilience, readiness, and retirement.(66) A growing prevalence imposes a substantial financial strain on the Department of Defense (DOD). A 2007 study estimated that TRICARE Prime spends $1.1 billion annually on obesity-related health care among active-duty and their dependents, along with an additional $61 million due to early separation from service and $103 million in lost workdays.(67) More recent data show thatthe cost burden has continued to rise, with obesity among active-duty Service members now estimated to exceed $1.65 billion annually, $1.25 billion in direct care costs, and $99 million in lost productivity from hospitalizations alone in 2023.(61) There is an increased prevalence of overweight or obesity among Veterans compared to the general U.S. population. In 2017, obesity prevalence ranged from 28% to 49% across 140 VHA facilities.(68) Veterans are 12% more likely to have overweight or obesity per data from 2003-2019.(69) In a retrospective study evaluating the BMI of Veterans enrolled within 90 days ofmilitary discharge and followed for 10 years, it was found that one-third of Veterans had a BMI in the overweight or obesity range upon enrollment, and after 10 years, more than 98% of the population had a weight gain of 22% to 40%.(70) The Veteran population also faces a heightenedrisk of obesity-related chronic diseases, including arthritis, diabetes mellitus, cancers, chronic heart disease, and kidney disease. Obesity has a profound impact on Veterans' physical health, increasing risk for chronic disease, while also negatively impacting mental health and quality of life.(71,72) ## C. Impact of Weight Loss on Obesity-associated Conditions Clinically meaningful weight loss has long been defined as 5% from baseline, as this threshold has been shown to improve glycemic control, triglyceride levels, blood pressure, and high-density lipoprotein cholesterol (HDL-c) levels. However, increasing evidence demonstrates that greater weight loss leads to progressively more substantial health benefits.(11,73-75) Weight loss of atleast 10% is often required for meaningful improvements in obstructive sleep apnea and MASLD, while metabolic dysfunction-associated steatohepatitis (MASH) requires 10-40% weight loss to show improvements in liver inflammation and fibrosis.(75,76) For patients with type 2 diabetes,weight loss exceeding 15% is frequently associated with remission of diabetes.(11) Additionally,cardiovascular benefits, including reductions in hypertension, dyslipidemia, and cardiovascular events, are more pronounced with weight loss exceeding 10-15%.(11,73) In the realm of ### Page 12 reproductive health, at least 10% weight loss is often necessary to improve female infertility, whereas male hypogonadism shows improvements with 5-10% weight loss. Osteoarthritis benefits from at least 5-10% weight loss, while gastroesophageal reflux disease (GERD) typically requires 10% or more to see symptom relief.(11,73) While modest weight loss can improvemetabolic markers and lower healthcare costs, greater weight loss leads to superior outcomes across multiple obesity-related conditions, reinforcing the importance of individualized weight loss goals beyond the traditional 5% benchmark.(77,78) In this guideline, we selected weight loss as a critical outcome for evaluating weight management interventions for overweight and obesity, largely because most studies on lifestyle modifications, pharmacotherapy, and bariatric surgery use the magnitude of weight loss as a primary measure. However, as our understanding of obesity as a complex disease evolves, it is clear that the percentage of weight loss alone does not provide the full picture. Weight loss metrics fail to capture crucial changes in body composition, specifically, whether individuals are losing fat mass, muscle mass, or both. More importantly, the distribution of fat loss matters. The reduction of visceral fat, which is strongly linked to adiposopathy or dysfunctional fat tissue, is particularly important, as it drives chronic inflammation, insulin resistance, dyslipidemia, and cardiovascular disease. Future research should place greater emphasis on body composition and fat distribution to better assess the metabolic benefits of weight management interventions. Additional information on assessment, clinical workflows, operational considerations in active-duty Service members, team-based roles, and suggested follow-up appears inAppendix O. # III. Scope of This Guideline This CPG is based on clinical evidence and related information published from April 1, 2019, to January 6, 2025. It is intended to provide general guidance on evidence-based best practices (seeAppendix A for additional information on the evidence review methodology). Although the CPG isintended to improve the quality of care and clinical outcomes (seeIntroduction), it is not intendedto define a standard of care (i.e., mandated or strictly required care). ## A. Guideline Audience This CPG is designed to assist providers in managing or co-managing patients with overweight and/or obesity. ## B. Guideline Population This CPG is for adults with overweight and obesity. # IV. Highlighted Features of This Guideline ## A. Highlights in This Guideline Update The current document is an update to the 2020 VA/DOD OBE CPG. The major strength of this CPG is the coordination and collaboration of the multidisciplinary team, ensuring a broad ### Page 13 representation of providers engaged in overweight and obesity management. The following significant updates make it important that providers review this version of the CPG: - • UpdatedAlgorithm; - • UpdatedPharmacotherapy section; - • Recommendations: added 8 new, reviewed and replaced 4, reviewed and amended 7, and carried over 4 unchanged. The methodology used in developing this CPG has been updated since the prior versions and reflects a more rigorous application of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The result is a refined CPG that includes methodologically rigorous, evidence-based recommendations for the management of adults with overweight and/or obesity. This CPG also provides expanded recommendations on research needed to strengthen future guidelines. ## B. Components of This Guideline This CPG provides clinical practice recommendations for the care of patients with overweight and obesity (seeRecommendations). In addition, theAlgorithm incorporates the recommendations inthe context of the flow of patient care. This CPG also includesResearch Priorities, which list areasthe Work Group identified as needing additional research. To accompany this CPG, the Work Group also developed toolkit materials for providers and patients, including a provider summary, a patient summary, and a quick reference guide, which can be found at:[https://www.healthquality.va.gov/index.asp](https://www.healthquality.va.gov/index.asp). ## C. Demographic and Other Terminology in This Guideline The demographic terms in this guideline are based on the published literature sources included in the systematic review (SR) and evidence base. The Work Group used terms like Black rather than African American and White rather than Caucasian to avoid presumptions about ancestry and enhance clarity and consistency. In order to accurately present the research evidence on which this CPG is based, the Work Group made every effort to use the same terminology as reported in the published literature base of SRs, clinical trials, and other studies. Consequently, usage of demographic terms in this CPG may vary and appear inconsistent. For the purposes of thisdocument, we have deliberately and consistently used the term “Obesity Medications” for medicalclarity. This reflects the use of these medications in healthcare settings to address the disease ofobesity. “Weight Management Medications,” however, is the preferred terminology for patient- centered communication and public health messaging to avoid stigmatizing language. # V. Guideline Development Team The VA Evidence Based Practice, Office of Quality and Patient Safety, in collaboration with the Clinical Quality Improvement Program, Defense Health Agency, identified the following fourproviders to serve as Champions (i.e., leaders) of this CPG’s Work Group: Stéphanie B. Mayer, ### Page 14 MD, MHSc, Dipl. ABCL, Dipl. ABOM and Susan Raffa, PhD, FSBM from VA; and Elizabeth M. Bauer, MD, FACP, FACE Dipl. ABOM and Richele Corrado, DO, MPH, FACP, Dipl. ABOM from DOD. The Work Group comprised individuals with the following areas of expertise: bariatric surgery, behavioral medicine, dietetics, endocrinology, gastroenterology, medical nutrition therapy, mental health, nursing, obesity medicine, pharmacy, physical therapy, population health, preventive medicine, and primary care.Table 1lists the Work Group and Guideline DevelopmentTeam members. This CPG Work Group, led by the Champions, was tasked with: - • Determining the scope of the CPG; - • Crafting clinically relevant key questions (KQ) to guide the systematic evidence review; - • Identifying discussion topics for the patient focus group and considering the patient perspective; - • Providing direction on inclusion and exclusion criteria for the systematic evidence review and the assessment of the level and quality of evidence; and - • Developing evidence-based clinical practice recommendations, including determining the strength and category of each recommendation. The Sigma Team (Sigma Health Consulting and Duty First Consulting) was contracted by VA to help develop this CPG. ### Page 15 Table 1. Guideline Work Group and Guideline Development Team ### Page 16 *Additional contributor contact information is available inAppendix D # VI. Summary of Guideline Development Methodology The methodology used in developing this CPG follows the Guideline for Guidelines, an internal document of the VA/DOD EBPWG updated in January 2019 that outlines procedures for developing and submitting VA/DOD CPGs.(79) The Guideline for Guidelines is available at[http://www.healthquality.va.gov/policy/index.asp](http://www.healthquality.va.gov/policy/index.asp). This CPG also aligns with the National Academyof Medicine’s (NAM) principles of trustworthy CPGs (e.g., explanation of evidence quality andstrength, management of potential conflicts of interest [COI], interdisciplinary stakeholder involvement, use of SR and external review).(80)Appendix A provides a detailed description ofthe CPG development methodology. ## A. Evidence Quality and Recommendation Strength The Work Group used the GRADE approach to craft each recommendation and determine its strength. Per the GRADE approach, recommendations must be evidence based and cannot be made based on expert opinion alone. The GRADE approach uses the following four domains to inform the strength of each recommendation (seeDetermining Recommendation Strength andDirection).(81) - 1. Balance of desirable and undesirable outcomes - 2. Confidence in the quality of the evidence - 3. Patient or provider values and preferences - ### Page 17 - - - - 4. Other implications, as appropriate (e.g., resource use, equity, acceptability, feasibility, subgroup considerations) Using these four domains, the Work Group determined the relative strength of each recommendation (Strong or Weak). The strength of a recommendation is defined as the extent to which one can be confident that the desirable effects of an intervention outweigh its undesirable effects and is based on the framework above, which incorporates the four domains.(82) A Strongrecommendation generally indicates High or Moderate confidence in the quality of the available evidence, a clear difference in magnitude between the benefits and harms of an intervention, little variability in patient values and preferences, and limited concerns about the influence of other implications (e.g., resource use, feasibility). In some instances, insufficient evidence exists on which to base a recommendation for or against a particular therapy, preventive measure, or other intervention. For example, the systematic evidence review might have found little or no relevant evidence, inconclusive evidence, or conflicting evidence for the intervention. The way this finding is expressed in the CPG might vary. In such instances, the Work Group might include among its set of recommendations a statement of insufficient evidence for an intervention that might be in common practice, although it is unsupported by clinical evidence, and particularly if other risks of continuing its use might exist (e.g., high opportunity cost, misallocation of resources). In other cases, the Work Group might decide to exclude this type of statement about an intervention. For example, the Work Group might remain silent where an absence of evidence occurs for a rarely used intervention. In other cases, an intervention might have a favorable balance of benefits and harms but might be a standard of care for which no recent evidence has been generated. Using these elements, the Work Group determines the strength and direction of each recommendation and formulates the recommendation with the general corresponding text as shown inTable 2. Table 2. Strength and Direction of Recommendations and General Corresponding Text It is important to note that a recommendation’s strength (i.e., Strong versus Weak) is distinct fromits clinical importance (e.g., a Weak recommendation is evidence based and still important to clinical care). The strength of each recommendation is shown inRecommendations. This CPG’s use of GRADE reflects a more rigorous application of the methodology than previousiterations; the determination of the strength of the recommendation is more directly linked to the confidence in the quality of the evidence on outcomes that are critical to clinical decision making. ### Page 18 The confidence in the quality of the evidence is assessed using an objective, systematic approach independent of the clinical topic of interest. Therefore, recommendations on topics for which designing and conducting rigorous studies might be inherently more difficult (e.g., randomized controlled trials [RCT]) are typically supported by lower quality evidence and, in turn, Weak recommendations. Recommendations on topics for which rigorous studies can be designed and conducted might more often be Strong recommendations. Per GRADE, if the quality of evidence differs across the relevant critical outcomes, the lowest quality of evidence for any of the critical outcomes determines the overall quality of the evidence for a recommendation.(5,83) This stricterstandard provides a consistent approach to determining recommendation strengths. For additional information on GRADE or CPG methodology, seeAppendix A. ## B. Categorization of Clinical Practice Guideline Recommendations Evidence-based CPGs should be current. Except for an original version of a new CPG, stayingcurrent typically requires revision of a CPG’s previous versions based on new evidence or asscheduled subject to time-based expirations.(84) For example, the U.S. Preventive Services TaskForce (USPSTF) has a process for monitoring the emergence of new evidence that could prompt an update of its recommendations, and it aims to review each topic at least every five years for either an update or reaffirmation.(85) Recommendation categories were used to track how the previous CPG’s recommendations couldbe reconciled. These categories and their corresponding definitions are similar to those used by the National Institute for Health and Care Excellence (NICE, England).(86,87)Table 3 lists thesecategories, which are based on whether the evidence supporting a recommendation wassystematically reviewed, the degree to which the previous CPG’s recommendation was modified, and whether a previous CPG’s recommendation is relevant in the updated CPG. Additional information regarding these categories and their definitions can be found inRecommendation Categorization. The 2025 CPG recommendation categories can be found inRecommendations.Appendix C outlines the 2020 VA/DOD Overweight and Obesity CPG’srecommendation categories. Table 3. Recommendation Categories and Definitions* ### Page 19 *Adapted from the NICE guideline manual (2012) (86) and Garcia, et al. (2014)(87) Abbreviation: CPG: clinical practice guideline ## C. Management of Potential or Actual Conflicts of Interest Management of COIs for the CPGs is conducted as described in the Guideline for Guidelines.(79)Further, the Guideline for Guidelines refers to details in the VHA Handbook 1004.07 Financial Relationships between VHA Health Care Professionals and Industry (November 2014, issued by the VHA National Center for Ethics in Health Care)(88) as well as to disclosure statements (i.e.,standard disclosure form completed at least twice by CPG Work Group members and the guideline development team).(79) The disclosure form inquiries regarding relevant financial andintellectual interests or other relationships with, for example, manufacturers of commercial products, providers of commercial services, or other commercial interests. The disclosure form also inquires regarding any other relationships or activities that could be perceived to haveinfluenced, or that give the appearance of potentially influencing, a respondent’s contributions tothe CPG. In addition, instances of potential or actual COIs among the CPG Work Group and the guideline development team were subject to random web-based identification via standard electronic means (e.g., Centers for Medicare & Medicaid Services Open Payments, ProPublica). ## D. Patient Perspective When developing a CPG, consideration should be given to patient perspectives and experiences, which often vary from those of providers.(83) Focus groups can be used to help collect qualitativedata on patient perspectives and experiences. VA and DOD Leadership arranged a virtual patient focus group on November 21, 2024. The focus group aimed to gain insights into patient perspectives of adult patients with overweight and/or obesity who have received care in the VA and DOD healthcare systems and incorporate these insights into the CPG, as appropriate. Topics discussed included screening and management of overweight and obesity in the VA and DOD healthcare systems, including patients’ weight loss treatment history, preferences for care delivery setting and transitions, priorities and treatment challenges, as well as the impact their weight and treatment have had on their lives. The Patient Focus Group, which may include up to nine patients (i.e., subject to the Paperwork Reduction Act), was comprised of a convenience sample of five participants, which included four women and one man. Participants were mixed in terms of receiving care from VA or DOD, with one participant also receiving care from Kaiser Permanente. The participants were also mixed in terms of being active-duty Service members and Veterans. Three participants reported receiving ### Page 20 treatments in the form of obesity medications, starting within the last two years. For more information on the patient focus group methods and findings, seeAppendix E. The patient focusgroup participants were provided with the opportunity to review the final draft of this CPG and provide additional feedback. ## E. External Peer Review The Work Group drafted, reviewed, and edited this CPG using an iterative process. For more information, seeDrafting and Finalizing the Guideline. Once the Work Group members completeda near-final draft, they identified experts from VA and DOD health care systems and outside organizations generally viewed as experts in the respective field to review it. The draft was sent to those experts for a 14-business-day review and comment period. The Work Group considered all feedback from the peer reviewers and modified the CPG where justified, in accordance with the evidence. Detailed information on the external peer review can be provided by the VA Office of Quality and Patient Safety. ## F. Implementation This CPG is intended for adaptation by individual healthcare providers, considering local services, resources, and capacity (professional, administrative, and logistical). The algorithm serves to inform providers of key decision points throughout the complex long-term management of overweight and obesity; both of these chronic medical conditions require long-term management with similar resource allocation to other chronic illnesses, such as diabetes and HTN. The Work Group aims to widely disseminate these evidence-based weight management recommendations to improve the health and well-being of Veterans and Service members. To this end, the Work Group has produced supplemental educational materials: a provider summary and pocket card for practitioners, and a patient summary for patients. The VA and DOD have specific plans for the dissemination and implementation of CPGs. This CPG is sent to several focused email groups within the VA and DOD systems for dissemination. Newly released CPGs are presented on quarterly calls to chief medical officers nationally within the VA system. VA/DOD CPGs are presented at various national professional society conferences and published in respected peer-reviewed medical journals. CPGs are posted to national/international guideline clearinghouses, available free of charge, and submitted to frequently consulted online medical resources, including epocrates® and UpToDate®, to broaden dissemination. The CPG aims to inform the VA and DOD about the efficacy of combined weight loss tools, specifically comprehensive lifestyle intervention programs (e.g., VA’s MOVE!® Weight Management Program for Veterans [MOVE!], pharmacologic treatments, and metabolic/bariatric surgical interventions. Nationwide harmonization of these weight loss interventions across VA and DOD healthcare facilities will improve quality of life and reduce obesity-related conditions for Veterans and Service Members. Operationalization of these recommendations to achieve efficient coordinated management of overweight and obesity across the system nationally and across service lines is of great ### Page 21 importance. We must first establish that the management of overweight and obesity is an organization-wide priority and allocate adequate resources to effectively treat Service members and Veterans with overweight/obesity, particularly as therapeutic interventions continue to evolve. Next is the need to track patient, program, and population-level achievement of clinically meaningful outcomes. System-wide integration will ensure access to overweight and obesity care across VA and the DOD. This integration will promote effective care coordination, stratification by level of patient risk, and patient engagement strategies. System-wide integration is clearly needed to implement an evidence-based, multicomponent approach to weight management.(89) Although this CPG represents the recommended practices on the date of its publication, medical practice is evolving and requires ongoing awareness by providers and policymakers alike of newly published information. New technology and additional research will improve patient care in the future. This CPG can assist in identifying priority areas for research and informing the optimal allocation of resources. Future studies examining the results of CPG implementation may lead to the development of new evidence, particularly relevant to clinical practice and resource allocation. ### Page 22 # VII. Approach to Care in the Department of Veterans Affairs and the Department of Defense ## A. Patient-Centered Care Intended to consider patient needs and preferences, guideline recommendations represent a whole/holistic health approach to care that is patient-centered, culturally appropriate, and available to people with varied literacy skills and physical, sensory, or learning abilities. VA/DOD CPGs encourage providers to use a patient-centered, whole/holistic health approach (i.e., individualized treatment based on patient needs, characteristics, values, and preferences). This approach aims to treat the condition while optimizing the individual’s overall health and well-being. Regardless of the care setting, all patients should have access to individualized, evidence-based care. Patient-centered care can decrease patient anxiety, increase trust in providers, and improve treatment adherence.(90,91) A whole/holistic health approach ([https:/www.va.gov/wholehealth/](https://www.va.gov/wholehealth/))empowers and equips individuals to meet their personal health and wellbeing goals. Good communication is essential and should be supported by evidence-based information tailored toeach patient’s needs. An empathetic and non-judgmental approach facilitates discussions sensitive to sex, culture, ethnicity, and other differences. The 5 As of obesity management (seeTable 4) is a structured, patient-centered framework for effective communication about obesitycare adapted from behavioral counseling models. This approach helps clinicians engage patients in respectful, nonjudgmental conversations about weight, assess health risks and contributing factors, provide clear and personalized treatment recommendations, set collaborative goals, and ensure appropriate support and follow-up. Using the 5 As aligns obesity care with chronic disease management principles, promotes shared decision-making, and supports individualized, evidence-based treatment plans to improve health outcomes. Table 4. The 5 As Framework of Obesity Management (92) ### Page 23 Abbreviations: BMI: body mass index ## B. Shared Decision Making This CPG encourages providers to practice shared decision making, a process in which providers, patients, and family/friend/caregiver consider clinical evidence of benefits and risks as well aspatient values and preferences to make decisions regarding the patient’s treatment.(93) Shareddecision making is emphasized in Crossing the Quality Chasm, an Institute of Medicine report from 2001(94), and is a core component of a holistic health approach. Providers must be adept atpresenting information to their patients regarding individual treatments, expected risks, expected outcomes, and levels or settings of care, or both, especially where patient heterogeneity in weighing risks and benefits might exist. The Veterans Health Administration and the Military Health System have embraced shared decision-making. Providers are encouraged to use shared decision-making to individualize treatment goals and plans based on patient capabilities, needs, and preferences. ## C. Patients with Co-occurring Conditions Co-occurring health conditions are important to recognize because they can contribute to the risk of developing overweight and obesity, impact the management of overweight and obesity, influence patient or provider treatment priorities and clinical decisions, and affect the overall provider approach to the management of overweight or obesity. Providers should expect that many Veterans, Service members, and their families will have one or more co-occurring health conditions. Because overweight and obesity management often takes place in parallel with ### Page 24 ongoing care for co-occurring conditions and can be affected by the treatment of other conditions, especially pharmacologic choices, it is generally best to manage overweight and obesity collaboratively with other care providers. When caring for patients with overweight or obesity, a careful review of their medication list may reveal medications that promote weight gain and are counterproductive to patient weight loss efforts (see). Some co-occurring conditionsmay require early specialist consultation to coordinate necessary changes in treatment and/or to establish a common understanding of how care will be coordinated and delivered. VA/DOD CPGs exist for Chronic Insomnia Disorder/OSA1 1 See the VA/DOD Clinical Practice Guideline for the Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea. Available at:[https://www.healthquality.va.gov/guidelines/CD/insomnia/index.asp](https://www.healthquality.va.gov/guidelines/CD/insomnia/index.asp), Chronic Kidney Disease (CKD)2 2 See the VA/DOD Clinical Practice Guideline for the Management of Chronic Kidney Disease. Available at:[https://www.healthquality.va.gov/guidelines/CD/CKD/](https://www.healthquality.va.gov/guidelines/CD/CKD/), Diabetes Mellitus3 3 See the VA/DOD Clinical Practice Guideline for the Management of Type 2 Diabetes Mellitus in Primary Care. Available at: [https://www.healthquality.va.gov/guidelines/CD/diabetes/](https://www.healthquality.va.gov/guidelines/CD/diabetes/), Hypertension4 4 See the VA/DOD Clinical Practice Guideline for the Diagnosis and Management of Hypertension in the Primary Care Setting. Available at:[https://www.healthquality.va.gov/guidelines/CD/HTN/](https://www.healthquality.va.gov/guidelines/CD/HTN/), and Major Depressive Disorder (MDD)5 5 See the VA/DOD Clinical Practice Guideline for the Management of Major Depressive Disorder. Available at: [https://www.healthquality.va.gov/guidelines/MH/mdd/](https://www.healthquality.va.gov/guidelines/MH/mdd/). SeeAppendix O,Sidebar 4, andSidebar3for guidance regarding the medical assessment of patients with overweight and obesity. ### Page 25 # VIII. Algorithm This CPG includes an algorithm that is designed to facilitate understanding of the clinical pathways and decision-making processes used in managing patients with overweight or obesity. The use of the algorithm format as a way to represent patient management was chosen based on the understanding that such a format may promote more efficient diagnostic and therapeutic decision making; it also has the potential to change patterns of resource use. Although the Work Group recognizes that not all clinical practices are linear, the simplified linear approach depicted through the algorithm and its format allows the provider to assess the critical information needed at the major decision points in the clinical process. It includes: - • An ordered sequence of steps of care - • Recommended observations and examinations - • Decisions to be considered - • Actions to be taken The algorithm is a step-by-step decision tree. Standardized symbols are used to display each step, and arrows connect the numbered boxes, indicating the order in which the steps should be followed.(95) Sidebars provide more detailed information to assist in defining and interpretingelements in the boxes. ### Page 26 ## Algorithm Module ![Algorithm Module. Step-by-Step decision tree]() a See, for example, 2020-2025 Dietary Guidelines for Americans, 9th edition, available at:[Dietary Guidelines forAmericans](https://www.dietaryguidelines.gov/) and Physical Guidelines for Americans, 2nd Edition, available at:[Physical Activity Guidelines for Americans| odphp.health.gov](https://odphp.health.gov/our-work/nutrition-physical-activity/physical-activity-guidelines) b Waist circumference: ≥102 cm (40 in) for men and ≥88 cm (35 in) for women, for those of Asian descent: ≥90 cm (35.4 in) for men and ≥80 cm (31.5 in) for women or waist-to-hip ratio (WHR) >0.90 for men and >0.80 for women. , or waist-to-height ratio (WtHR)(96) ≥ 0.50 for all c The waist circumference measurement should be made with a tape measure placed around the bare abdomen just above the iliac crest. The tape should be snug, but should not compress the skin, and the measurement should be obtained while the patient is standing at the end of normal exhalation(97) d For patients of Asian descent: is BMI ≥23 kg/m2?;(98) for patients >65 years old: consider individualizedassessment(99) ### Page 27 e The Fibrosis-4 (FIB-4) index(100) is a non-invasive scoring system used to estimate liver fibrosis based on severallaboratory tests Abbreviations: BMI: body mass index; CLI: comprehensive lifestyle intervention; CMP: comprehensive metabolic panel; DOD: Department of Defense; VA: Department of Veterans Affairs; WHR: waist-to-hip ratio; WtHR: waist-to-height ratio ### Page 28 ![Sidebar 1: Principles and Core Strategies of Motivational Interviewing and Behavioral Counseling $Grouped Object$]() a See information for Behavioral Counseling Interventions, available at:[Behavioral Counseling Interventions: AnEvidence-based Approach | United States Preventive Services Taskforce](https://www.uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes/behavioral-counseling-interventions-evidence-based-approach) Sidebar 2: Select Medications and their Potential Effects on Weighta Providers will need to individualize recommendations to their patient ### Page 29 ### Page 30 ### Page 31 a The information provided in the table is not to be considered all-inclusive and is a compilation of information from the medical literature (systematic reviews, meta-analyses, subgroup analysis of clinical trials, cohort studies, reviews), some of which may have included differing comparators with variable results based on length of follow-up, baseline weight, patient comorbidities, etc.; medical and pharmacy resources; and select product information (adverse events, post-marketing and case reports). b Weight gain and weight loss have been reported. *should there be more description of initial vs. long-term effects on weight* for beta blockers: Bakris GL, Fonseca V, Katholi RE, et al. Metabolic Effects of Carvedilol vs Metoprolol in Patients With Type 2 Diabetes Mellitus and Hypertension: A Randomized Controlled Trial. JAMA. 2004;292(18):2227–2236. doi:10.1001/jama.292.18.2227(103) c High basal insulin (≥ 0.5units/kg) can cause sub-clinical hypoglycemia that can increase appetite (see Clinical Care Note in Introduction to the 2025 OBE CPG Pharmacotherapy Recommendations) d See Table D-3: Antipsychotic Adverse Event Profiles in the April 2023 VA/DOD Clinical Practice Guideline for Management of First-Episode Psychosis and Schizophrenia. Available at:[https://www.healthquality.va.gov/guidelines/MH/scz/](https://www.healthquality.va.gov/guidelines/MH/scz/) e See Table J-2: Antidepressant Adverse Event Profiles in the February 2022 VA/DOD Clinical Practice Guideline for the Management of Major Depressive Disorder. Available at:[https://www.healthquality.va.gov/guidelines/MH/mdd/](https://www.healthquality.va.gov/guidelines/MH/mdd/) f Lopez LM, Ramesh S, Chen M, et al. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016(8):CD008815.(104); Gallo MF, Lopez LM, Grimes DA, Carayon F, Schulz KF, Helmerhorst FM. Combinationcontraceptives: effects on weight. Cochrane Database Syst Rev. 2014(1):CD003987.(105) Abbreviations: ARB: angiotensin receptor blocker; ARV: antiretroviral; GLP-1: glucagon-like peptide-1 receptor; HTN: hypertension; MAOI: monoamine oxidase inhibitor; NSAID: nonsteroidal anti-inflammatory drug; SGLT2: sodium-glucose cotransporter 2 ### Page 32 - • Endocrine conditions (e.g., Prediabetes and Diabetes Mellitus, Metabolic Syndromeb) - • Cardiovascular conditions (e.g., ASCVD, HTN, Dyslipidemia, Atrial Fibrillation, CHF, Stroke) - • Gastrointestinal conditions (e.g., MASLD, GERD) - • Musculoskeletal (e.g., OA/degenerative joint disease) - • Mental health conditions (e.g., depression, PTSD, anxiety, disordered eating) - • Respiratory conditions (e.g., OSA, asthma, hypoventilation syndrome) - • Genitourinary conditions (e.g., PCOS, female infertility, male hypogonadism, stress incontinence) - • Renal (e.g., microalbuminuria, CKD) - • Cancer(1-3) - • Neurological (e.g., IIH) See Appendix X for more detail (Adiposopathy and Mass effect) add to title and make two columns Add a note that it is not a comprehensive list Sidebar 4: Common Overweight- & Obesity-Associated Conditions By Systema - • Assess for presence of obesogenic medications (see on pharmacotherapy) - • Assess for factors associated with overweight or obesity if physical exam and personal family history warrant, including but not limited to: depression, eating disorders or disordered eating, food insecurity and nutritional insufficiency, menopause, endocrine disorders (e.g., hypothyroidism, acromegaly, hypogonadism, hypercortisolism), neurologic conditions (e.g., hypothalamic obesity, traumatic brain injury, brain tumor, cranial irradiation, spinal cord injury), sleep apnea Sidebar 3: Assessment of Factors Associated with Obesity a This list of conditions is not a comprehensive list of overweight and obesity associated conditions. b See National Cholesterol Education Program definition of metabolic syndrome, available at:[https://www.nhlbi.nih.gov/files/docs/guidelines/atglance.pdf](https://www.nhlbi.nih.gov/files/docs/guidelines/atglance.pdf) Abbreviations: ASCVD: atherosclerotic cardiovascular disease; CHF: congestive heart failure; CKD: chronic kidney disease; GERD: gastroesophageal reflux disease; HTN: hypertension; IIH: idiopathic intracranial hypertension; MASLD: metabolic dysfunction-associated steatotic liver disease; OA: osteoarthritis; OSA: obstructive sleep apnea; PCOS: polycystic ovarian syndrome; PTSD: post-traumatic stress disorder - • Defined as an intervention that combines behavioral, nutritional, and physical activity components together (seeRecommendation 2,Recommendation 6,Recommendation 8,Recommendation 9,andAppendix O) - • The intervention can be delivered in an individual or group setting, in person, by telephone, or through synchronous video (seeRecommendation 2,Recommendation 4,Recommendation 5, andAppendix O) - • Though there is insufficient evidence to recommend a specific number of sessions of comprehensive lifestyle intervention, most CLIs offer at least 12 intervention sessions in the first 12 months of intervention (seeRecommendation 2) Sidebar 5: Comprehensive Lifestyle Intervention Abbreviations: CLI: comprehensive lifestyle intervention ### Page 33 Abbreviations: BMI: body mass index; kg: kilograms; m: meters The thresholds listed below are for the initiation of therapy. These medications may be continued for maintenance of BMI target goals. Consider for long-term pharmacotherapy (seeAppendix J): - • Patients with a BMI ≥30 kg/m2 - • Patients with a BMI ≥27 kg/m2 and an obesity-related comorbidity (seeTable J-1) - • Individualize choice of medication to patient-specific comorbidities, dosing, administration, and potential for side effects NOTE: Patients with BMI≥25-27 kg/m2 with additional adiposity measures require special considerations. SeeRecommendations for further information. Sidebar 6: Assessment for Pharmacotherapy *Use Asian population cutoffs perTable O-2 Consider for endoscopic and/or bariatric therapies (seeRecommendation 11,Recommendation 13, andAppendix K: - • For intragastric balloons, patients with a BMI of 30-40 kg/m2 - • For endoscopic sleeve gastrectomy, patients with a BMI of 30-50 kg/m2 Sidebar 7: Assessment for Endoscopic and/or Bariatric Therapies Abbreviations: BMI: body mass index; kg: kilograms; m: meters Consider for metabolic/bariatric surgery (seeRecommendation 12 andAppendix K): - • Patients with a BMI ≥30 kg/m2 and T2DM - • Patients with a BMI ≥35 kg/m2 Sidebar 8: Assessment for Metabolic and/or Bariatric Surgery Abbreviations: BMI: body mass index; kg: kilograms; m: meters; T2DM: type 2 diabetes mellitus ### Page 34 # IX. Recommendations The evidence-based clinical practice recommendations listed in the table below were developed using a systematic approach considering four domains as per the GRADE approach (seeSummary of Guideline Development Methodology). These domains include confidence in thequality of the evidence, balance of desirable and undesirable outcomes (i.e., benefits and harms), patient values and preferences, and other implications (e.g., resource use, equity, acceptability). Table 5. Evidence-Based Clinical Practice Recommendations with Strength and Category ### Page 35 ### Page 36 a For additional information, please refer toDetermining Recommendation Strength and Direction b For additional information, please refer toRecommendation Categorization ### Page 37 Recommendation - 1. There is insufficient evidence to recommend either for or against a particular measure of adiposity to manage clinical outcomes in patients with overweight or obesity. (Neither for nor against | Reviewed, New-added) Discussion A summary of the various methods for measuring body composition is presented inAppendix M.Data comparing the accuracy of one modality to another exists, however, there is minimal data on the clinical utility of using these various modalities to define excess adiposity and improve clinical outcomes. One cross-sectional study of 3,675 participants compared dual-energy x-ray absorptiometry visceral adipose tissue (DXA-VAT) to standard anthropometric measurements(body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio [WHtR]) found that DXA-VAT was not superior for predicting diabetes.(106) In the samestudy, as well as an additional cross-sectional observational study, the DXA-VAT was found to be superior to BMI, WC, WHR, and WHtR for the prediction of cardiometabolic risk factors, specifically low HDL-C, raised BP, triglycerides, HbA1c, and metabolic syndrome, compared to BMI, with some variances between DXA-VAT and DXA-VAT/total fat ratio. WC was also superior to BMI.(106,107) One study showed that for each standard deviation (SD) increase inDXA-VAT, there was an associated fourfold increase in odds for females and a fivefold increase in odds for males of having metabolic syndrome (MetS). After adjusting for BMI, WC, or WHR, the DXA-VAT remained independently predictive, with adjusted odds ratios (ORs) of 2.5-3.5 per standard deviation (SD) change. The prediction cut-point for MetS was approximately 900g in females and 1600g in males.(107) While these cross-sectional observational studies providesome evidence, the lack of higher-quality studies, poor study quality of the retrieved studies, higher costs, lower feasibility, and higher resource usage are reasons why the Work Group found insufficient evidence to recommend for or against using specific measures of adiposity. Although a specific modality of measurement cannot be recommended, body composition can aid in the evaluation of excess adiposity, specifically visceral adiposity, help risk-stratify individuals with an elevated BMI, and identify those with a lower BMI who have low lean muscle mass. Additionally, special groups such as military personnel and athletes who have prolonged physical training and higher physical requirements are more likely to have higher muscle mass, which can lead to overdiagnosis of overweight and obesity. This was demonstrated in a study of female Marines, where comparing BMI and body adiposity index to DXA scans revealed significant individual variability, and on average, the BMI predicted body fat can be off by nearly 5%.(108) A study of varsity male and female athletes found that a BMI of 25 or greater overdiagnosed excess adiposity, with a specificity of 27% and 66% in diagnosing excess adiposity, but it had 100% sensitivity in both groups. The optimal BMI cut point in this group was calculated to be closer to 28 kg/m² in both groups and 34.1 kg/m² in male linemen.(109)Conversely, there is also substantial evidence that BMI can underdiagnose excess adiposity in both the general and special populations. A meta-analysis of 32 research studies from 12 countries found a pooled sensitivity of only 50% in diagnosing excess adiposity with a specificity of 90%. Although high, this specificity indicates that using only BMI can lead to a misdiagnosis of excess adiposity in 10% of people, while this low sensitivity will miss the diagnosis of excess ### Page 38 adiposity in 50% of people.(110) In a study of over 3,800 Brazilian military firefighters, BMIunderestimated the prevalence of obesity, with a sensitivity of ≤ 67%, indicating BMI missed over one-third of true cases. Specificity, the ability of BMI to correctly rule out non-obese individuals, was ≥81.2%.(111) Body composition can provide a more accurate measure ofadiposity, thereby avoiding misdiagnosis and treatment strategies that are directed at weightreduction when it is not needed. Another area where body composition analysis would be beneficial is in monitoring the decrease in fat-free mass (FFM) (lean mass) and fat mass during weight loss. With weight loss, average FFM loss typically ranges between 5% and 35% of the total weight lost. The degree of loss depends on several factors, including age, sex, the amount of body fat present before weight loss, and whether caloric restriction and/or exercise were part of the weight loss regimen, among others. Still, it is unclear if physical function, such as muscle strength, is affected.(112)Additional studies are needed to examine the use of body composition modalities in helping to decrease skeletal muscle mass (SMM) loss associated with large amounts of weight loss and todetermine if physical function is affected. As this is a Reviewed, New-added recommendation, the Work Group systematically reviewed evidence related to this recommendation.(106,107) Overall, the evidence investigating thecomparative clinical utility of various modalities and measures of body composition in defining and managing excess adiposity and improving clinical outcomes is minimal, with only cross- sectional observational studies retrieved in the data review. Additionally, none of the studies reviewed directly reported the outcomes of interest. The body of evidence had several limitations and confounders, including the poor methodological quality of cross-sectional studies, unclear inclusion criteria, homogeneity of the population, and unclear variations in exposures, which collectively led to the overall low Strength of Evidence (SOE) for the outcomes assessed. The Work Group concluded that the evidence was insufficient to favor a particular measure of adiposity for managing clinical outcomes in individuals with overweight and obesity. However, the evidence reviewed suggested that DXA-derived VAT may be associated with a better identification of cardiometabolic diseases, such as metabolic syndrome (primarily characterized by elevated triglycerides, low high-density lipoprotein) and diabetes (elevated fasting blood glucose, HbA1c), in comparison to anthropometric measures like body mass index, waist circumference, and waist-to-hip ratio. Consequently, using body composition methods to assess visceral adiposity may provide better identification of those at increased metabolic risk and could be more beneficial than relying solely on standard anthropometric measures or BMI forrisk stratification and treatment evaluation. Thus, the Work Group decided upon a Neither for nor against recommendation. ### Page 39 Recommendation - 2. We recommend offering an in-person group or individual comprehensive lifestyle intervention that always includes behavioral, dietary, and physical activity components for patients with overweight or obesity. (Strong for | Not reviewed, Not-changed) - 3. We suggest offering a comprehensive lifestyle intervention for weight maintenance to patients who have completed a comprehensive lifestyle intervention for weight loss. (Weak for | Not reviewed, Not-changed) - 4. We suggest offering an individual or group telephone-delivered comprehensive lifestyle intervention for weight loss, either as an alternative to or in conjunction with an in-person intervention. (Weak for | Not reviewed, Not-changed) - 5. There is insufficient evidence to recommend either for or against a specific number of sessions, or a specific technology (except for telephone, see Recommendation 4), as the primary mode of delivery of a comprehensive lifestyle intervention. (Neither for not against | Reviewed, New-replaced) Discussion We define comprehensive lifestyle interventions (CLI) for weight loss and weight maintenance as interventions that combine three critical lifestyle components (i.e., behavioral, dietary, and physical activity) in a structured curriculum or protocol(113) and aim to produce a negative energy balance.CLI is the term used in the 2014 and 2020 VA/DOD Obesity CPGs, other recent CPGs, and evidence reviews of weight management interventions.(9,114) In this guideline, we define “in-person” as an intervention that necessitates the patient’s and provider’s physical presence ratherthan telephone or synchronous interactive video, or synchronous online chat or text. The 2014 VA/DOD Obesity CPG found that CLIs produced clinically significant weight loss amongpatients with overweight or obesity. CLIs were recommended as “central to successful and sustained weight loss” and, more specifically, as a primary intervention to achieve weight loss and improve obesity-associated conditions in adults with overweight or obesity. For the 2020 VA/DOD Obesity CPG, a 2018 systematic review of CLIs commissioned by the U.S. Preventive Services Task Force (USPSTF) identified 80 good or fair quality randomized controlled trials (RCTs) of CLIs for weight loss (n=30,394 adults with overweight or obesity).(115) Findings were alsopublished in a 2018 article from the Journal of the American Medical Association.(116) Resultsfrom 67 of the RCTs (n=22,065) indicated greater weight loss from CLIs compared to minimal intervention or usual care control conditions at 12 – 18 months (mean difference [MD] in weight change: -2.39 kg; 95% confidence interval [CI]: -2.86 to -1.93).(115) Moreover, interventionparticipants had a 1.94 times greater probability of losing 5% of their initial weight over 12 – 18 months compared with the control group, which translated into a number needed to treat of eight.(115) Additionally, at 24 months, the pooled risk ratio (RR) of achieving a 5% weight loss ### Page 40 was 1.51 (95% CI: 1.25 to 1.81), and the pooled RR of a 10% weight loss at 12 – 18 months was 3.06 (95% CI: 2.41 to 3.88). For all weight loss outcomes, there is moderate confidence in the quality of evidence.(115) Weight outcomes beyond 24 months are rarely studied or reported. A2011 systematic review(117) found that patients, on average, regain a third of lost weight within 1year of treatment ending, thus the importance of offering maintenance interventions (see evidence discussed in CLI for Weight Maintenance section below). The 2018 USPSTF systematic review also examined the impact of CLIs versus control conditions on a variety of health outcomes, although studies that focused on a specific chronic disease for which weight loss/maintenance is part of disease management (e.g., cardiovascular disease (CVD), HTN, DM) were excluded.(115) Across nine trials (n=3,140) that evaluated the impact ofCLIs compared to control conditions among individuals with overweight and obesity selected for baseline impaired fasting glucose, the pooled RR of developing incident DM was 0.67 (95% CI: 0.51 to 0.89).(115) Within these, the two largest, good quality studies (n=1,817 combined) thatfocused on the prevention of DM (the Finnish Diabetes Prevention Study [n=522])(118,119) andthe Diabetes Prevention Program Outcomes Study [n=1,295])(120) showed an absolute riskreduction of developing type 2 diabetes mellitus (T2DM) of approximately 14.5% over 3 – 9 years, as described in the 2018 USPSTF systematic review.(115) Evidence on the long-term impact of CLIs versus control conditions on the prevalence of HTN, metabolic syndrome, use of cardiovascular disease (CVD) medications, and 10-year risk of CVD was limited to a small number of trials or was inconclusive and limited or inconsistent on the long- term impact of CLIs on all-cause mortality, cardiovascular (CV) events, and quality of life (QoL).(115) CLIs delivered in studies evaluating long-term health outcomes generally lasted foronly 1 – 2 years, limiting the ability to assess an effect on these outcomes. Moreover, both observational studies and controlled trials in populations with specific chronic conditions have demonstrated that a 5% weight loss produces clinically significant improvements in these conditions.(9) We recommend both group and individual in-person modalities for delivering CLIs. Subgroup analyses performed for the 2018 USPSTF systematic review found no pattern of effects on the main outcome of weight change at 12 – 18 months follow-up according to the main mode of intervention delivery (i.e., group versus individual versus technology-based versus mixed)(115),though, as discussed below, there were limitations to the evidence for the technology-based interventions included in the systematic review. Other intervention characteristics (e.g., intervention duration, the number of sessions in the first year) did not modify the effect of the intervention on change in weight(115) (See discussion ofevidence for the number of intervention sessions below). Additional subgroup analyses found that the mean baseline weight category (i.e., overweight, Class 1 obesity, Class 2 obesity) was not associated with differences in effects on weight change,(115) supporting the Work Group’srecommendation of CLI for weight loss for patients with overweight as well as obesity. However, the heterogeneity of the interventions and differences in the populations, settings, and trial quality made it difficult to identify which variables may be associated with larger effects.(115) ### Page 41 As noted above, CLIs combine behavioral, dietary, and physical activity components that aim to produce a negative energy balance. Although the evidence reviewed does not allow us to recommend any specific constellation of behavioral strategies for achieving clinically significant weight loss, the behavioral component of the CLIs included in the 2018(115) and the 2011USPSTF systematic reviews(121) usually included the following elements: setting weight loss,physical activity, and dietary goals; self-monitoring (e.g., weighing, physical activity, and calorie/food tracking); stimulus control; cognitive strategies; identifying barriers to change; problem solving; relapse prevention; peer support; and in-treatment support.(115,121) These elements arealso emphasized in other reviews of CLIs for weight loss. Most interventions provided tools to assist with weight loss (e.g., pedometers, food scales, exercise videos), and 12 of the CLIs included an explicit motivational interviewing component to promote participant follow-through with CLI sessions and use of behavioral strategies.(122) For more information about specificapproaches and behavioral strategies commonly included in CLI, seeAppendix L andAppendixO. See also recommendations and discussions on physical activity (Recommendation 8 andRecommendation 9) and dietary components (Recommendation 6 andRecommendation 7). Despite the high heterogeneity found across the 80 CLIs in the 2018 USPSTF systematic review, the consistency in effects seen across specific interventions and various adult subgroups emphasizes a broad range of benefits from CLIs. The heterogeneity found across studies is likelyrelated to unmeasured individual, social, and environmental factors influencing an individual’sweight loss, rather than specific intervention characteristics.(115) The 2014 VA/DOD Obesity CPG Work Group found that offering a maintenance CLI that includes behavioral, dietary, and physical activity components with ongoing support reduces the likelihood of weight regain.(114,121,123) The 2018 USPSTF systematic review (n=2,704) compared CLIsfor weight maintenance after weight loss to no interventions (four trials), minimal intervention (three trials), or usual care (two trials). The systematic review included RCTs of participants with pre-intervention body mass index (BMI) ≥25 kg/m2 who reported weight or adiposity change at least 12 months following the start of the weight maintenance intervention. Interventions included group or individual counseling sessions delivered by phone, in-person, or through technology. The interventions were designed to help study participants maintain weight loss by continuing a healthy diet, physical activity, and use of behavioral strategies (seeAppendix K andAppendix O).The frequency and intensity of interventions were variable. In most studies, the duration of the maintenance intervention was 12 – 18 months and included 12 – 26 sessions in the first year. The SR found a significant difference favoring the intervention versus controls (eight studies, n=1,408) in maintenance of previous weight loss.(115) Results of one included trial (n=1,029) alsofavored the intervention group regarding continued maintenance of ≥5% weight loss at 30 monthspost-intervention and 60 months post-intervention. Although there are relatively few maintenance trials and the net benefit is small, three of the maintenance trials included some participants who were not successful in meeting initial weight loss goals, limiting the likelihood of finding a significant difference in maintained weight loss between maintenance intervention conditions versus control conditions. The 2018 USPSTF systematic review also determined there is insufficient evidence to favor group or individual treatment. ### Page 42 As noted in Recommendation 2, the Work Group recommends offering an in-person group or individual CLI to patients with overweight or obesity for weight loss to prevent or improve obesity- associated conditions. Based on the evidence reviewed in the 2014 and 2020 VA/DOD Obesity CPGs, the Work Group suggests offering telephone-based CLI for weight loss to support long- term weight management, either as an alternative to or in conjunction with a face-to-faceintervention. “In conjunction with” is defined as in addition to another intervention, while “an alternative” is defined as in place of an intervention. As detailed in Recommendation 2, a 2018 USPSTF systematic review of 80 RCTs of CLIs for weight loss demonstrated greater weight loss from CLIs compared to minimal intervention or usual care control conditions.(115) Fifteen of these RCTs tested CLIs that included a telephone-delivered component. Investigators examined the effects of intervention modality on weight loss outcomes produced by CLI and found no significant difference in the magnitude of effects between in-person versus telephone modalities. Two fair-quality RCTs, not included in the 2018 USPSTF systematic review, directly compared the impact of telephone-delivered versus face-to- face CLIs on weight loss outcomes and found no significant differences between the intervention conditions.(124,125) Based on this evidence, the Work Group concluded that telephone-deliveredCLI is effective as an alternative to face-to-face CLI and in conjunction with face-to-face CLI (i.e., when used to increase the total number of sessions attended.(114,115,124,125) As described in Recommendation 2, we recommend offering an in-person group or individual CLI to patients with overweight or obesity for weight loss to support long-term weight management and to prevent or improve obesity-associated conditions. The Evidence Synthesis Report generated for this update of the VA/DOD CPG found that, overall, the evidence assessing the comparative effectiveness of CLIs for overweight or obesity, including CLIs of different intensities, is sparse and based exclusively on single trials, each comparing different types of CLIs, except for a single trial comparing varying exercise intensities in the same CLI (seeRecommendation 8 andRecommendation 9). While the 2014 VA/DOD Obesity CPG recommended offering at least 12 sessions of a CLI within 12 months, based on the evidence reviewed at that time, review of additional studies for the 2020 VA/DOD CPG led to the conclusion that there is insufficient evidence to recommend offering a specific number of sessions to produce significant weight loss. However, the evidence also suggests that CLIs that offer at least 12 sessions in the first 12 months of intervention produce a larger and more consistent effect on weight loss at 12 – 18 months of follow-up than CLIs that offer fewer than 12 sessions in the first 12 months. As detailed in Recommendation 2, a 2018 USPSTF systematic review of 80 RCTs of CLIs for weight loss demonstrated greater weight loss from CLIs compared to minimal intervention or usual care control conditions.(115) To examine the effect of intervention intensity on weight lossoutcomes, investigators who conducted the 2018 USPSTF systematic review abstracted the total number of sessions conducted in the first 12 months for each intervention arm.(115) Sessions ### Page 43 were defined as any group or individual counseling session conducted face-to-face or by telephone, or any web- or computer-based module or session.(115) When the number of sessionswas examined as a continuous measure, a higher number of intervention sessions in the first 12 months was associated with significantly more weight loss (coefficient: -0.03; p=0.023).(115)However, the number of sessions in the first year was not associated with greater weight loss after controlling for the presence of group sessions (coefficient: -0.015; p=0.212). Moreover, when intervention intensity was examined in a subgroup analysis according to the number of intervention sessions in the first year (>26 sessions, 12 – 26 sessions, and <12 sessions), results showed significantly greater effects versus controls for all three subgroups. Although there were larger effect estimates among interventions with more sessions in the first 12 months of intervention, the CIs across all three of the subgroups overlapped, so these differences were not statistically significant. Although there was no significant difference found for the number of sessions in the first 12 months of intervention, almost two-thirds (n=44) of the 67 interventions included in the analysis of weight loss at 12 – 18 months offered at least 12 sessions within the first year of the intervention.(115) Also, the absence of a significant difference for number of sessions in the firstyear was likely influenced by the inclusion of eight technology-based trials in the 0 – 11 session subgroup that offered a high volume of additional contacts (through mobile phone text messages, emails, or interactions with other web-based or social media platforms) to supplement the sessions. Moreover, the quality of the evidence for a differential impact based on the number of CLI sessions was rated as low due to the large clinical and statistical heterogeneity of the CLIs included in the SR and the lack of studies directly evaluating the impact of the number of sessions on weight loss outcomes while controlling for other intervention characteristics.(115) Although the Work Group concluded that there is insufficient evidence to recommend a specific number of CLI sessions in the first 12 months of a CLI, the larger effect sizes found for CLIs that offer 12 – 26 sessions (MD: -2.48 kg), or >26 sessions (MD: -3.06 kg), when compared to <12 sessions (MD: -1.73 kg), are meaningful differences and suggest CLI intensity matters. Moreover, the American Heart Association/American College of Cardiology/The Obesity Society Guideline for the Management of Overweight and Obesity in Adults, published in 2013, strongly recommended providing a high-intensity CLI (≥14 sessions in the first six months).(9) The Evidence Synthesis Report generated for this update of the VA/DOD CPG found that, overall, the evidence assessing the comparative effectiveness of CLIs for overweight or obesity is sparse and based exclusively on single trials, each comparing different types of CLIs. There was no evidence identified comparing the efficacy of different delivery modes for the administration of CLIs. No relevant systematic reviews were identified due to most systematic reviews on this topic failing to include CLIs that met our requirements of including behavioral, dietary, and physical activity components, inclusion of participants with additional disorders above the ≤15% thresholdused in this review, or assigning heterogeneous CLIs to the same comparator condition. As noted in Recommendation 2, we recommend offering an in-person group or individual CLI to patients with overweight or obesity for weight loss to support chronic weight management and to ### Page 44 prevent or improve obesity-associated conditions. However, there was insufficient evidence to recommend for or against offering a technology-delivered CLI either as an adjunct or alternative to CLI delivered in-person or by telephone. Support for this recommendation is based on the evidence review conducted for the 2020 VA/DOD Obesity CPG. As detailed in above, a large 2018 USPSTF systematic review included RCTs of studies that used technology as the main mode of intervention for CLI, along with trials that featured other CLI delivery modalities (i.e., individual, group, mixed).(115) Subgroup analyses found no consistentpattern of effects on weight loss outcomes according to the main mode of intervention delivery on change in weight, suggesting technology-delivered interventions were effective.(115) However,the MD in weight loss outcomes favoring the 12 technology-delivered interventions versus control was small (MD: -1.14 kg; 95% CI: -1.59 to -1.09), especially considering the MD between CLI versus control for all 67 trials included in the primary analysis (-2.39 kg; 95% CI: -2.86 to -1.93). Moreover, the 12 studies of technology-delivered CLIs(126-137) included in the 2018 USPSTFsystematic review identified a wide range of technologies employed across the trials. Seven(126,128,131,132,135-137) of the 12 individual trials did not find a significant differencebetween intervention and minimal intervention or usual care control groups on weight loss at 12 –18 months. One of the five positive trials focused on post-partum weight loss(133) another wasfound to be effective in men but not women(134) and two explicitly described face-to-face,interactive components.(126,131) Most of the other trials included some form of humaninteraction, making it difficult to determine the degree to which the technology component of the intervention contributed to outcomes. Though the systematic evidence review conducted as part of this guideline update did not identify any studies that specifically evaluated the impact of synchronous video-delivered CLI, this intervention modality is likely to be as efficacious as telephone-delivered CLI. The visual cues offered by synchronous video-delivered CLI may enhance provider-patient communication and thereby enhance patient engagement in the intervention. Evidence indicates the risk of harm from CLI is low. Rates of adverse events were reported in 27 trials (n=12,235) among the 80 behavior-based weight loss trials included in the 2018 USPSTF systematic review.(115) There were no serious harms related to the interventions, and most trialsnoted no differences between groups in the rates of adverse events, including CV events.(115)Musculoskeletal events were most commonly related to the intervention groups, although only one trial found a statistically significant difference in events across intervention and control groups. In the Diabetes Prevention Program trial (n=2,161), a statistically significant increased rate of musculoskeletal symptoms (e.g., myalgia, arthritis, arthralgia) was seen among those in the lifestyle intervention group (24.1 events per 100 person-years) compared with those in the control group (21.1 events per 100 person-years) (p<0.0167) over four years of follow-up.(120) Althoughthere is some burden to patients when participating in a CLI that includes multiple clinical contacts over many months or weeks, the benefits are significant, and there are many options for participating in effective interventions, including telephone-delivered counseling and video- telehealth programming that may attenuate the burden. ### Page 45 The Patient Focus Group that was convened for this CPG update highlighted the value of non- pharmacological therapies and lifestyle changes when managing overweight and obesity. Moreover, the focus group participants emphasized the importance of goal setting, having an individualized treatment plan, and having a coach or provider to provide support and accountability. These patient preferences and values are aligned with the elements and approach inherent in the delivery of CLIs and the findings that a variety of modalities, including group, individual, and mixed modalities, are effective for weight loss. The Work Group also notes that there are limitations in offering a weight management intervention that features many sessions, including the large variability in the way patients wish to receive their sessions. Some may prefer a CLI that includes fewer sessions, while others may prefer one that includes a greater number of sessions. Additionally, some subgroups of patients may be unable to participate in CLIs that require many sessions (e.g., a patient who is limited by transportation, telephone availability, or lack of a computer). CLI session number and frequency may also be limited by healthcare facility constraints, such as a lack of staff and space, and an inability to provide the interventions in accordance with all patient preferences. Lastly, there are differences in the ability of VA and DOD programs to provide CLIs of greater intensity. In the VA, the MOVE! program, which meets the criteria for a CLI, has already been integrated into clinical practice, increasing resources devoted to CLIs. No comparable agency-wide standardized voluntary weight management program has been consistently adopted across the DOD, which may present a challenge for many DOD locations. It may also be less feasible for some groups of patients (e.g., rural Veterans, soldiers who are deployed or on temporary field training) to access a maintenance CLI. Despite general consistency in the evidence supporting telephone-based CLI, there is some variability in patient preferences regarding this modality. CLI can be burdensome to patients, as CLI requires frequent contacts. For certain populations, telephone-delivered intervention may be less feasible (e.g., patients with hearing impairment or unreliable phone service). Furthermore, there may be limited access to telephone-based CLI, as there are relatively few providers who have been trained in CLI or have dedicated time for telephone-delivered interventions. While telephone-delivered CLI may increase access to care, and patients may feel more comfortable and less self-conscious, it can be difficult to obtain clinical measurements over the phone. Although the Work Group found insufficient evidence to recommend for or against the use of technology as a primary means to deliver CLIs, it is important to consider variation in patient values and preferences, efficiency of resource utilization, and potential reach of interventions. Patients vary in their desire or preference for technology-delivered interventions; for some patients, a technology-delivered intervention may increase their access to lifestyle interventions. While these interventions may reduce the burden and travel time related to in-person intervention, the use of technology may introduce burdens as well, which vary depending on the type of technology. In terms of equity, while most Service members and Veterans have access to smartphones, data plans vary, and not all individuals have access to all types of technology. Also, individuals in rural or remote locations may not have the same opportunity to benefit from technology-based interventions when infrastructure lags in these areas. ### Page 46 The Work Group did not systematically review evidence related to Recommendation 2, but did consider evidence from the prior VA/DOD CPG.(115) Therefore, it is categorized as NotReviewed, Not Changed. The Work Group’s confidence in the quality of the evidence wasmoderate. The body of evidence had some limitations, including heterogeneity of interventions, few trials reporting differences in weight change at longer follow-up, and few trials reporting the baseline CV risk status of participants.(115) The benefits of CLI (e.g., clinically important weightloss), outweighed the potential harm of minor musculoskeletal events, which were small. Patient values and preferences varied somewhat because patients vary in their ability to access CLI and attend numerous sessions. Thus, the Work Group decided upon a Strong for recommendation. The Work Group did not systematically review evidence related to Recommendation 3, but did consider evidence from the prior VA/DOD CPG.(115,124,138) Therefore, it is categorized as NotReviewed, Not Changed. The Work Group’s confidence in the quality of the evidence wasmoderate. The body of evidence had some limitations, including a small number of trials reporting 5% weight loss and one trial with wide confidence intervals(115); however, all nine trials reviewedin the 2018 USPSTF systematic review were rated fair or good quality. The benefits of maintenance CLIs for maintenance of weight loss outweighed the potential harm of minor adverse events, e.g., musculoskeletal symptoms. Patient values and preferences somewhat varied as discussed in the preceding paragraph. Thus, the Work Group decided upon a Weak forrecommendation. The Work Group did not systematically review evidence related to Recommendation 4, but did consider evidence from the prior VA/DOD CPG(115,124,125) Therefore, it is categorized as a NotReviewed, Not Changed. The Work Group’s confidence in the quality of the evidence was low.The body of evidence had some limitations, including the fact that no good-quality RCTs were identified that directly compared telephone to face-to-face modalities while controlling for other characteristics of the CLI. The benefits of weight loss outweighed any potential harm, which is minimal for CLIs as discussed above. Patient values and preferences were varied because some patients prefer in-person interventions, and telephone participation may be less feasible for some (e.g., patients with hearing impairment or unreliable phone service). Thus, the Work Group decided upon a Weak for recommendation. The Work Group systematically reviewed evidence related to Recommendation 5(139-141) andconsidered the evidence put forth in the 2020 VA/DOD CPG.(115) Therefore, it is categorized asReviewed, New-replaced. The Work Group’s confidence in the quality of the evidence was verylow. The body of evidence had significant limitations, including poorly defined and heterogeneous interventions, minimal intervention or no treatment controls, weight loss outcomes at less than 12 months of follow-up, high attrition, lack of blinding of patients and providers, and small sample sizes(115,139-141) The benefits of having options for how (i.e., modality) and how intensely (i.e.,number of sessions) an individual participates in CLI outweigh the potential harm associated with participation in CLI described above. Patient values and preferences were similar because patients want flexibility in how they participate in CLI. Thus, the Work Group decided upon aNeither for nor against recommendation. ### Page 47 Recommendation - 6. We recommend offering patients a dietary approach that contributes to a negative energy balance to achieve weight loss as the dietary component of a comprehensive lifestyle intervention. (Strong for | Reviewed, Not-changed) Discussion A negative energy balance occurs when energy expenditure exceeds energy intake, resulting in the body utilizing stored energy and leading to weight loss. A dietary approach that achieves a negative energy balance and promotes weight loss in patients with overweight and obesity remains a core component of comprehensive lifestyle interventions (CLI) (seeAppendix H forspecific dietary approaches and guidance).(115,142-153) A 2018 USPSTF systematic review of80 RCTs of CLIs for weight loss demonstrated greater weight loss from CLIs that included a dietary component compared to minimal intervention or usual care control conditions.(115) Anegative energy balance to support weight loss can be achieved through a variety of dietary approaches.(142-164) The importance of providing a caloric deficit was first explored in the Overweight/Obesity CPG from the VA/DOD in 20141 1 Request the 2014 VA/DOD Clinical Practice Guideline for the Management of Obesity and Overweight. Available at:[https://www.healthquality.va.gov/CPGArchives.asp](https://www.healthquality.va.gov/CPGArchives.asp) and was carried forward by the 2020 CPG Work Group. In order to maintain a Strong for recommendation, we looked back at the data from the 2014 CPG.(165-175)The 2014 studies compared dietary approaches to usual care, while the evidence pulled for the 2025 CPG consisted of studies comparing dietary approaches to each other. The quality of the 2025 evidence ranged from very low to moderate. The 2025 evidence reinforced the weight loss effect provided by a calorie deficit, as all the dietary approaches reviewed achieved weight loss via a negative energy balance. Even though the studies were comparative, there was a weight loss trend in all the dietary approaches reviewed in the 2025 evidence, which we felt reinforced conclusions made from the 2014 evidence.(154-164) The concept of negative energy balance, essential to the success of a comprehensive lifestyle intervention, has been extensively explored with varying levels of evidence regarding its role in weight loss and health. The evidence from the 2014 review, rated as moderate, highlights the effectiveness of dietary interventions in achieving weight loss, supported by studies that investigated the impact of caloric restriction and macronutrient composition on energy balance.(165-175) The 2014 CPG supports the use of calorie restriction for weight loss,recommending a daily caloric deficit of 500-750 kcal for effective weight management. The 2020 evidence further contributed to the field, while recent comparative effectiveness studies from 2025 continue to explore the different impacts of negative energy balance through various dietary and lifestyle interventions.(154-164) These studies reinforce the importance of individually tailoringstrategies to effectively achieve energy balance and improve health. ### Page 48 Though not required, access to a registered dietitian nutritionist can help with navigating a desired dietary approach and ensuring that a negative energy balance is achieved, while limiting micronutrient deficiency. Limitations in access to the services of a registered dietitian nutritionist by Active-duty military personnel and Veterans could affect their ability to implement and sustain effective dietary strategies. Addressing access barriers to these services is important to support the health and well-being of these individuals. Ultimately, the best dietary approach is one to which the patient can adhere. The benefits of a dietary approach with a negative energy balance outweigh potential harms. Overall, there is no evidence of harm to patients in achieving a modest negative energy balance.(142-153,165-176) Ketogenic diets can lead to increases in low-density lipoprotein (LDL)but also high-density lipoprotein (HDL) and more significant reductions in triglycerides (TG).(158)Patients following a ketogenic diet will benefit from additional monitoring and support. Elevations in LDL-C may be clinically significant in some patients and should be balanced against other options for calorie-restricted diets, especially in patients at risk for atherosclerotic cardiovascular disease. Patient harm is possible if a very low-calorie diet (≤800 kcal) is used for a prolonged period of time due to effects from sarcopenia and decreased bone density, particularly in postmenopausal women.(148,163,177) The Work Group systematically reviewed evidence related to this recommendation.(154-175)Therefore, it is categorized as Reviewed, Not changed. The Work Group’s confidence in thequality of the evidence was moderate. The body of evidence had some limitations, including that the 2025 study pull included studies with very low-quality evidence, but since this was based on comparisons of one dietary approach to another rather than comparison to a placebo, we looked back to the data from 2014 to carry forward this recommendation. The benefits of offering patients a dietary approach that contributes to a negative energy balance through comprehensive lifestyle intervention outweigh the potential harm and adverse effects from specific dietary choices. Patient values and preferences were similar because patients prefer guidance and choice on effective diets that will help them with weight loss. Thus, the Work Group decided upon a Strong forrecommendation. Recommendation - 7. For weight loss and weight maintenance, there is insufficient evidence to recommend either for or against a particular dietary approach and/or strategy over another. (Neither for not against | Reviewed, New-replaced) Discussion When considering dietary interventions for weight loss and weight maintenance, current evidence suggests that no single dietary approach is superior to others. However, dietary approaches may have differing impacts on other health outcomes. All diets reviewed can effectively contribute to weight loss through a caloric deficit.(154-164) However, theireffectiveness is a product of patient adherence and, when adhered to, actual influence on total caloric intake. However, their effectiveness is a product of patient adherence and, when adhere to, actual influence on total caloric intake, which may both be driven by patient preference. The ### Page 49 approaches in the current review included calorie tracking, meal replacements, low-fat, low glycemic, low carbohydrate, ketogenic, vegetarian dietary patterns, and several methods of intermittent fasting. Offering a variety of dietary approaches for those seeking weight loss is important to ensure individualized patient care. The importance of access to various dietary choices that are considered personal preferences was highlighted by participants in the patient focus group. These concerns can affect both active military Service members and Veterans, who may have limited choices due to deployment locations or socioeconomic factors. Dietary approaches such as a ketogenic diet may be more expensive or less readily available. A dietary approach such as intermittent fasting can offer flexibility, providing relief from the rigidity of traditional calorie counting, but for some can lead to overconsumption or excess hunger. To effectively implement a chosen diet, it is desirable to have the guidance of a registered dietitian nutritionist. Registered dietitian nutritionists can provide education, support skill building, evaluate nutritional adequacy, and ensure that dietary changes are both safe and effective. Certain dietary approaches may not be suitable for all populations. For instance, severe energy restriction in post- menopausal women has been associated with greater loss of total hip bone mineral density compared to moderate energy restriction.(163) Some dietary approaches, particularly ketogenicand vegetarian diets, may lead to nutritional deficiencies and therefore require individualized guidance. Some dietary approaches offer a negative energy balance without the need for strict calorie counting, such as a ketogenic diet and intermittent fasting (IF). The Workgroup found evidence on the effectiveness of these approaches since the 2020 CPG; therefore wanted to highlight this information. A ketogenic or low-carbohydrate diet leads to a calorie deficit primarily through mechanisms of appetite suppression and reduced energy intake. A state of ketosis has been shown to suppress the secretion of ghrelin, the hunger hormone, and increase the release of satiety peptides like glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK).(178-180)Reduced feelings of hunger and increased feelings of fullness contribute to a lower overall caloric intake.(180,181) With IF, a negative energy balance is achieved primarily through the reduction ofoverall caloric intake and the metabolic adaptations that occur during fasting periods. IF regimens (see Appendix H), such as alternate-day fasting (ADF; defined as one fasting day or 25% of usualenergy intake, alternative with one ad libitum feeding day), the 5:2 diet (defined as fasting 2 days per week on nonconsecutive days with 5 feeding days per week), and time-restricted eating (TRE; defined as a shortened daily eating window which inherently limits the time available for eating), often lead to a reduction in total caloric intake.(154,155) Studies have shown that these regimenscan reduce energy intake by 10-30% from baseline, contributing to weight loss.(182,183) Duringfasting periods, the body depletes its glycogen stores and shifts to mobilizing fatty acids, which are then converted to ketones. This metabolic switch from glucose to fatty acid-derived ketones enhances fat oxidation and preserves muscle mass, further promoting a negative energy balance.(184) If the patient wishes to prioritize Hemoglobin A1c (HbA1c) improvement, a ketogenic diet showed more significant HbA1c reductions than other dietary patterns. The meta-analysis by ### Page 50 Choi et al. (2020) showed that in 14 RCTs, 7 of which only included subjects with diabetes, all achieved improvements in their average HbA1c reduction.(158) A ketogenic diet may be adesired option for rapid improvements in HbA1c for those seeking improved glycemic control before an elective procedure. The potential barriers of this dietary approach are that it requires special instruction as well as should be utilized with caution due to an increased risk for hypoglycemia, especially when a patient is taking a hypoglycemic agent (e.g., insulin, sulfonylureas, meglitinides, etc.). The meta-analysis by Choi et al. (2020) also showed a slight increase in low-density lipoprotein (LDL) cholesterol, but also an increase in high-density lipoprotein (HDL) and a reduction in triglyceride levels (TG).(158) On a ketogenic diet, patientswith diabetes experienced a significant drop in triglycerides (−35.1 mg/dL) and an increase in HDL cholesterol (+3.5 mg/dL); across all patients, triglycerides fell by −20.7 mg/dL and HDLrose by +1.9 mg/dL. However, total cholesterol and LDL increased overall (+6.8 mg/dL and +5.9 mg/dL, respectively), with greater increases seen in patients without diabetes (total cholesterol: +10.1 mg/dL, LDL: +9.2 mg/dL).(158) Adequate dietary instruction and assessment may benecessary to ensure this diet yields the desired weight loss and health benefits. Based on a systematic review (SR) of 23 randomized control trials (RCTs), meal replacements, either partial or total, continue to be an effective option for those seeking weight loss as they are a convenient way to achieve a caloric deficit.(142,159) The 2014 and 2020 CPGs included arecommendation with low-quality evidence designating a standalone recommendation for meal replacements. One study of 66 matched participants included in the 2014 VA/DOD CPG revealed equal weight loss between participants using meal replacements and participants using a structured weight-reduction diet.(185) Evidence indicates that meal replacements arenot harmful to patients.(142) The use of meal replacements as a dietary approach is notsuperior to other approaches when reviewing comparative effectiveness; therefore, it was the Work Group’s decision not to carry this forward as a standalone recommendation. The current recommendation has broadened the ability to offer a variety of dietary approaches.(185) The Work Group systematically reviewed evidence related to this recommendation(154-164)including the evidence put forth from the 2014(165-175) and the 2020 iterations of thisCPG.(115,142-153,176) Therefore, it is categorized as reviewed, new replaced. The WorkGroup’s confidence in the quality of the evidence was very low. The body of evidence had somelimitations, including several very low-quality studies.(158,159,161) The benefits of not limitingdietary choices for those seeking weight loss improve access, preference, nutritional value, individualization, and equity, which outweigh the potential harm of adverse events, which was small. Patient values and preferences were similar because this provides choices. Thus, the Work Group decided upon a Neither for nor against recommendation. Recommendation 8. We suggest physical activity of any type for weight management and other health outcomes, and as the physical activity component of a comprehensive lifestyle intervention. (Weak for | Reviewed, New-replaced) Discussion ### Page 51 The 2025 Work Group reaffirmed and expanded upon its 2020 CPG suggestion for the inclusion of physical activity in weight loss, weight maintenance, prevention of further weight gain, and promotion of health outcomes as a component of a comprehensive lifestyle intervention.(186-197) Specific to weight loss, the effects of physical activity in isolation were generally modestand below the minimally clinically important difference of 5%. (188) However, physical activity isa necessary component of all comprehensive lifestyle interventions recommended for patients with overweight and/or obesity. Even within control groups with increased physical activity, there were notable improvements in weight management and other health outcomes regardless of intensity, supervision, or mode of activity.(188-191) In an RCT by Letnes et al. (2022)(197),health outcomes for seniors engaged in supervised activity and a control group given recommendations to follow Norwegian guidelines for activity, both had notable improvements. This should be encouraging for patients who are hesitant to initiate. SeeRecommendation 2,regarding a comprehensive lifestyle intervention. Type of Physical Activity When choosing types of physical activity, sustainability is the most important consideration. As discussed throughout this guideline, patient preferences are key in reducing sedentary time and generally increasing physical activity. However, as discussed inRecommendation 9, there areways to optimize physical activity for weight loss, weight maintenance, prevention of further weight gain, and health outcomes. While changes in body composition differed between types of exercise(190) and intensity(191), there were mixed results in superiority for total weightloss(191,197), but health benefits resulted from all types of exercise.(186) Duration of exercise(length of intervention in weeks)(188,191) had a large impact on fat loss and body composition.Adherence and attrition were significant influences in outcomes and highlight the role of patient preference in choosing a favorable activity. In the Letnes et al. (2022) study(197), for example,participant adherence to assigned groups was around half, with the other half self-selecting preferred workout styles during the study. Authors noted across many studies that patients tended to prefer the shorter high-intensity interval training (HIIT)(188), and hybrid(190) styletraining vs. moderate-intensity continuous training (MICT) and combined training, respectively. Many also favored Zumba, which has a higher adherence rate.(195) Physical activity is also well-known to have positive effects on mental health and quality of life, which were emphasized in a meta-analysis by Carraça et al. (2021).(194) Any type of exercisehad large positive effects on quality of life with smaller positive effects on function, pain, vitality, and mental health. Some types of group exercise may have positive social effects, including increasing a patient’s sense of community; in other cases, some forms like Zumba may be amore enjoyable entry-level exercise. As described above and inRecommendation 9, there areincreased benefits to health outcomes and weight loss the longer an exercise intervention is undertaken. This emphasizes patient preference for adherence. Regarding all health benefits and potential harms or burdens from exercise, seeRecommendation 9. The Work Group also considered how patient values and preferences regarding physical activity interventions might impact the recommendation. See the same category inRecommendation 9andAppendix I. ### Page 52 The Work Group systematically reviewed evidence related to this recommendation.(115,120,186-205) Therefore, it is categorized as Reviewed, New-replacedrecommendation. The Work Group’s confidence in the quality of the evidence is very low. The body of evidence had some limitations, including limited studies of long duration, heterogeneity of definitions of exercise types, and differing measures of adiposity. The benefits of exercise on weight status, body composition, and general health outcomes outweighed the potential of musculoskeletal events, which were relatively minor. Patient values and preferences varied widely. Patients prefer different modalities of training, have differing access to equipment, and have differing time available for the intervention. Thus, the Work Group decided upon a Weak for recommendation. Recommendation 9. To optimize health outcomes, we suggest moderate to vigorous intensity aerobic exercise combined with resistance training. (Weak for | Reviewed, New-replaced) Discussion While the importance of any type of physical activity outweighs any one type, the Work Group did find ways in which patients can optimize outcomes.(186-197,206) While the general healthbenefits of physical activity are well-established, reviewed evidence shows a dose-dependent impact on both health and weight-related outcomes. It is important for clinicians to educate patients that these dose-response effects are nonlinear, with diminishing returns at very high levels of exercise and physical activity. Further, while physical activity is a required component of a CLI, diet should still be regarded as the primary component of a CLI for weight loss.(207-209) (SeeRecommendation 2, regarding a comprehensive lifestyle intervention. This wasunchanged from the 2020 CPG which may be referenced for the full narrative). Of note, our Work Group selected weight status as our primary outcome of interest due to the breadth of evidence utilizing this outcome measure. However, there are some limitations in using weight status for outcomes comparing exercise due to gains in fat-free mass (e.g., bone, muscle). Hence, measurements of body composition are also of considerable importance. Combined exercise performed at higher intensities, for example, more consistently resulted in changes in body composition than weight status. Type of Physical Activity The included studies sought to compare different types of exercise in isolation; however, there was significant heterogeneity in the way they were conducted. These studies grouped exercise into distinct categories: Resistance Training (RT) using machines, free weights, and bodyweight to increase strength and muscle mass, and aerobic training such as walking, cycling, and jogging, to increase cardiovascular function. These were further subdivided into intensity which may be based on perceived rate of exertion, or heart rate; interval training, a form of aerobic training including High Intensity Interval Training which is punctuated with recovery periods and higher intensities; continuous endurance training which is aerobic training at a constant pace, or heart rate; combined training which includes both resistance training and aerobic training ### Page 53 performed in separate workouts or in blocks within a workout session; and hybrid training which intermixes strength and aerobic training. However, these are loose categories, and RCTs within each review differed in protocols. For body composition, the evidence supports combined interventions that include aerobic and resistance training over either component alone. As an example of the discussion above, the systematic review by Hao et al compared aerobic exercise of different intensities to resistance training and combined exercise, with included RCT interventions from 4 weeks to greater than 12 weeks. Outcomes for reducing total weight were best with vigorous intensity (AE-V) at 4.33kg vs control. However, body composition measured through body fat (BF)% was most improved with high-intensity combined exercise (4.7% vs. control). Even still, included studies measuring only body mass index (BMI)(189) found optimized outcomes (-1.34 decrease in BMIvs. control) with high-intensity combined exercise, suggesting it is at least equal, if not better, for total bodyweight reduction. Low-moderate intensity combined training was best for reducing waist circumference (-7.14cm vs. control), but only because there was no study with high intensity as a comparator for this outcome. Hao et al. (2023) noted “a conservative attitude towards the result that combined low-moderate, moderate intensity aerobic/low-to-moderate load resistance (COM-LM) is the best type of exercise to improve waist circumference,” insteadof high intensity. In the Batrakoulis et al. (2022) systematic review(190), the findings “support previousrecommendations concerning the importance of combined training in reducing body mass andbody fat in individuals with excess adiposity.” The authors compared combined training(separating resistance training sessions from aerobic sessions) and hybrid training (combining them within the session) and found hybrid had better outcomes for reducing waist circumference (-3.98cm vs. -8.3cm vs. control respectively); whereas combined training had the best outcomes for body mass (-2.57kg vs. control), body fat %(-2.76 vs. control), and fat-free mass (1.62kg vs. control). Much of this is dependent on the outcomes measured from particular studies. Given large known differences in patient preferences when performing types of exercise, providers may recommend hybrid methods (e.g., CrossFit, Orangetheory), which may provide similar outcomes with less training time. In the Chavarrias et al. (2021) study of Zumba(195), of note,the highest reduction in total fat mass% among Zumba participants was observed when combining Zumba workouts plus bodyweight exercises, with a 3.37% decrease. The authors stated, “to be more effective, the Zumba training should be combined with other trainingmodalities such as strength training.” Combined training was also favored for psychological impacts.(194) Patients withoverweight/obesity reported better outcomes for self-esteem, life satisfaction, quality of life, and social function with combined training over other forms of exercise. Dose-Dependent Impacts Several exercise program variables influence the magnitude of outcome effect size, especially when compounded. These were exercise intensity, frequency of sessions per week, duration (weeks) of physical activity undertaken, modality of aerobic exercise, and duration of program. ### Page 54 Beginning with training intensity, increased vigor led to improvements in body composition, with larger impacts when undertaken for a longer period of time. For example, Guo et al. (2023) showed improvements in percent fat mass to be greater in high-intensity interval training (HIIT) vs moderate-intensity continuous training (MICT), but this was for durations longer than 6 weeks and at a frequency of >3 days per week. In smaller doses, the changes in body composition may have been too small to detect. Regarding the amount of exercise, duration of intervention, and weekly frequency were consistently shown to be dose dependent. When comparing the volume of activity, Guo et al. (2023) found significant effects of greater than 3 times per week (- 0.94cm in waist circumference) and a duration of longer than 6 weeks (-0.62% fat mass) for any intensity of aerobic exercise. Poon demonstrated significantly decreased body fat percentage(BF%) with any type of interval training over MICT; however, there was no difference in BMI. Interval trainees gained approximately 1.4kg of fat-free mass, which reduced outcomes in BMI. These were prominent in durations greater than 12 weeks (-1.10% vs MICT) but not significant in durations of less than 12 weeks. Outcomes were also better in patients with higher BMI and in those who cycled as the preferred modality.(191) They outperformed non-exercise controls aswell as MICT. This again explains the weak findings for weight status outcomes. Further, patients who prefer shorter times within workouts may be more amenable to HIIT-style exercise. Conversely, martial arts exercise of lower intensity, such as Tai Chi, was not superior to inactive controls for weight loss, which the authors noted still received non-activity interventions in most.(196) Additionally, age may impact the utility of intensity in aerobic exercise. In the Guo et al. (2023) systematic review(188), HIIT had better outcomes in young and middle-aged adults than MICT.This was the finding in Letnes et al. (2022)(197), where seniors had no difference between highintensity vs. moderate activity or against active controls for weight status outcomes. However, as described inRecommendation 8 only about half of the participants strictly adhered to theassigned groups. All physical activity, however, had beneficial health outcomes, which exhibited a dose-dependent relationship.(186) Some types of training (i.e., HIIT) are shorter per session than others (i.e., MICT), this was not directly compared. However, interventions in the Batrakoulis et al. (2022) study(190) generallyfound the following parameters for intervention types: - • Interval Training (85-95% HRmax, 2-3 days per week, 91 min/week) - • Hybrid Training (75-85% HRmax, 2-3 days per week, 128 min/week) - • Continuous Endurance Training (60-70% HRmax, 3-5 days per week, 176min/week) - • Combined Training (3-4 days per week, 187 min/week) - • Resistance Training (70-80% 1 Rep Max, 2-3 days per week, 126 min/week) These are comparable to the ACSM guidelines(210) of: - • Moderate-intensity aerobic activity for a minimum of 30 minutes, five times per week, or vigorous-intensity aerobic activity for a minimum of 20 minutes, three times per week - • Resistance exercises for the major muscle groups, a minimum of 2 times per week - ### Page 55 - - - • Flexibility exercises for the major muscle groups, a minimum of 2 times per week Health Outcomes Regarding all health benefits from exercise, they are numerous and beyond the scope of this guideline. However, in reviewing specific health outcomes from compared exercise, there were differing impacts, with a dose-dependent response generally demonstrated. Vigorous aerobic exercise (AE) had better outcomes than moderate AE for leptin, adiponectin, C-reactive protein (CRP), IL-6, TNF-alpha(186), and VO2 max(189,190), with HIIT being more effective thanMICT.(188,190,192,197) There was no difference in outcomes between HIIT and MICT for HDL,LDL, TC, A1c, and glucose. Data conflicted on impacts on triglycerides, with HIIT showing superiority over MICT(190) but not for older populations(197). Hybrid-type training (HYB),combined training (COM), and resistance training (RT) were most effective for elevating HDL; COM was highly effective for reducing LDL.(190) Combined training, whether traditional or in ahybrid format, was most effective for fasting glucose and fasting insulin.(190) In patients withmetabolic syndrome, combined training was beneficial for the largest amount of laboratory markers (TNF-A, CRP, IL-6, IL-10)(193), with aerobic exercise being nearly equal. The benefits of including physical activity were judged to outweigh the relatively minor potential harms. The full benefits are large and far-reaching, but are beyond the scope of this guideline. For the background on these benefits, please see the 2018 Physical Activity Guidelines for Americans 2nd Edition (PAGA).(211) In addition to the general health benefits of physicalactivity, there is evidence that patients with overweight and obesity are likely to benefit from increasing physical activity regardless of its impact on weight status. This includes the positive effects of increased physical activity on comorbid conditions associated with overweight and obesity(199,204,211,212) and related benefits/effects such as health-related QoL and self-efficacy/physical function.(205) For example, osteoarthritis, chronic pain syndromes, andhypertension (HTN) (among others) are responsive to the doses and types of physical activity included in CLIs for weight loss. The harms of physical activity are musculoskeletal events, although only one trial found a statistically significant difference in events across intervention and control groups.(120) Other potential harms include the burden of time and effort expendedto follow a physical activity program. The Work Group also considered how patient values and preferences regarding physical activity interventions might impact the recommendation. Patients often want specific information on practical steps for increasing physical activity to support weight loss and maintenance (seeAppendix E). The Work Group judged that both patients and providers might have largevariations in preferences for different kinds of physical activity. In addition, there are variations in constraints faced by different subgroups of patients, such as access to a gym or exercise spaces/equipment, preexisting musculoskeletal or other health-related conditions that limit activity ability, and proximity to safe outdoor activity options. In the evidence(191), cyclingtended to have superior outcomes, which was noted by authors as an option that may have lower risk for injury and less pain as a non-impact modality. Given that osteoarthritis is an associated comorbidity of obesity, a low-impact exercise may be a preferable option. Further, some patients mentioned a preference for exercise setups that saved time. For aerobic training, patients performing high-intensity interval training instead of moderate continuous interval ### Page 56 training had improved outcomes and time savings.(189) When combining aerobic training withresistance training, some patients may prefer hybrid training for time savings. Unlike conventional combined training, which separates resistance and aerobic exercises either within the same session or into different sessions, hybrid training integrates resistance and aerobic training together. This includes methods like mixed resistance training and aerobic training performed simultaneously or in a blended format.(190) The Physical Activity Guidelines forAmericans (PAGA) recommends choosing physical activity types that align with the patient’svalues, abilities, and preferences, as well as consideration of activities that are accessible andmore easily incorporated into the patient’s daily life (e.g., walking).(211) SeeAppendix Iforfurther details on approaches to physical activity. The Work Group systematically reviewed evidence related to this recommendation.(115,120,186-205) Therefore, it is categorized as Reviewed, New-replacedrecommendation. The Work Group’s confidence in the quality of the evidence is very low. The body of evidence had some limitations, including limited studies of long duration, heterogeneity of definitions of exercise types, and differing measures of adiposity. The benefits of exercise on weight status, body composition, and general health outcomes outweighed the potential of musculoskeletal events, which were relatively minor. Patient values and preferences varied widely; patients prefer different modalities of training, have differing access to equipment, and have differing time available for the intervention. Thus, the Work Group decided upon a Weak for recommendation. Recommendation - 10. We suggest offering cognitive behavioral interventions to individuals experiencing internalized weight bias and stigma. (Weak for | Reviewed, New-added) Discussion Internalized weight bias and stigma are defined as holding negative beliefs about oneself due to weight or size. These beliefs are associated with negative health outcomes, including obesity. Our recommendation is to offer interventions to reduce internalized weight bias and stigma in affected individuals. Here, cognitive behavioral interventions are used to describe a category of interventions that target maladaptive thoughts (e.g., I would be able to lose weight if I were stronger) and or behaviors that reinforce maladaptive thoughts (e.g., avoidance of social situations due to internalized weight stigma). It is critical to note that healthcare providers and systems can be sources of weight bias and discrimination(213) and thus, potential targets forintervention. However, the systematic literature review did not identify provider-level interventions with outcomes at the patient level, a requirement for the Clinical Practice Guideline (CPG). One systematic review(214), two randomized clinical trials (RCTs) (215,216), and one pilot RCT(217) provided the evidence for the internalized weight bias and stigma recommendation. Chewet al. (2023) was a systematic review and meta-analysis of studies examining the effectiveness of Acceptance and Commitment Therapy (ACT) on weight, eating behaviors, and psychological outcomes, including weight-related stigma. ACT is a third-wave cognitive behavioral therapy ### Page 57 that has been shown to improve mental and physical health conditions. Four studies were included in this systematic review(218-221) with sample sizes ranging from 17 to 79, samplesbeing solely or predominantly female, and treatments lasting 8-11 weeks/sessions. Two were pilots(220,221), two had waitlist conditions (219,221), one had a treatment-as-usual (TAU)condition(218), one had an active treatment comparison condition (standard behavioral weightloss [BWL])(220), and one had three treatment arms(221). Evidence from these four trials(considered 5 studies due to the three-treatment arm trial) favored ACT for reducing internalized weight stigma compared to waitlist, TAU, and standard BWL therapy at immediate post- treatment (SOE: Very low). Evidence from two additional RCTs (215,216) (N=72-105; withpredominantly female samples) comparing 6-month BWL interventions plus a stigma-reduction intervention to BWL alone to reduce internalized weight stigma favored BWL plus the stigma- reduction intervention at 26-46 weeks but found no difference between treatment groups at 72 weeks. (SOE: Very low). A final pilot study(217) compared a virtual lifestyle modificationintervention followed by a mindful self-compassion intervention or dietary education intervention for 6 months in 28 women, in which both treatment conditions had reductions in internalized weight stigma at post-treatment (SOE: Very low). It was determined that the benefits of this recommendation (e.g., potential to reduce internalized weight bias and stigma within patients, and to reduce weight bias and discrimination in providers through greater awareness of having interventions offered) outweighed the potential harms/burden (none noted). Data from the Patient Focus Group was factored into this recommendation. Participants reported feeling stigmatized and singled out for their weight, as well as having negative feelingsabout how weight affects one’s military career and promotion. Participants made connectionsbetween unrealistic weight standards and eating disorders and body dysmorphia. They reported that provider suggestions of weight loss interventions (e.g., obesity medication) led to embarrassment and shame. Participants additionally reported a lack of supportive guidance from providers, with most reporting that providers simply instruct them to lose weight as if the patient had not recognized or tried to lose weight. This approach made participants feel stigmatized and misunderstood, leading to diminished motivation to pursue weight loss. Both past experiences with judgment and present negative tone or stigmatizing language from providers worsened internalized weight stigma. This, in turn, resulted in a lack of confidence in and motivation for seeking weight management care. Being weighed was met with reluctance. Although waist circumference measurement may be important as another metric of adiposity beyond BMI, the intrusiveness of this method and potential harm as it relates to stigma, especially in light of the harms associated with mandatory military weigh-ins, may need to be considered. Focus group participants discussed the value of providers expressing empathy and patience when working with patients on weight loss and weight maintenance, and this was perceived as a motivator for weight management efforts. Resource use for this recommendation was deemed low. Implications for providing these interventions involve the potentially large need for intervention, provider training and resources, education and awareness about internalized weight stigma and its interventions, and space for ### Page 58 the interventions. The recommendation was deemed feasible and acceptable, and at this time, there are no known subgroup considerations. As this is a Reviewed, New-Added recommendation, the Work Group systematically reviewed evidence related to this recommendation from the systematic evidence review(214-217), as wellas four studies found in the Chew et al. (2023) systematic review and meta-analysis.(218-221)The Work Group’s confidence in the quality of evidence was very low. The body of evidencehad some limitations in that it was a small number of randomized trials (N=7), of which three were pilot studies. It was determined that the benefits of this recommendation (e.g., potential to reduce internalized weight bias and stigma within patients, and to reduce weight bias and discrimination in providers through greater awareness of having interventions offered) outweighed the potential harms/burden (none noted). Patient values and preferences varied somewhat (e.g., experiences of weight bias and stigma among participants, and support/lack of support from providers). Thus, the Work Group decided upon a Weak for recommendation. Recommendation - 11. For temporary weight loss, we suggest intragastric balloons, in conjunction with acomprehensive lifestyle intervention, in patients with a body mass index ≥30 kg/m2,adherent to FDA guidelines*(see narrative). (Weak for | Reviewed, Amended) Discussion Endoscopic bariatric therapies (EBT) are minimally invasive, endoscopic weight loss procedures performed with an endoscope in patients with obesity. Currently, there are two FDA-approved modalities that are commercially available. These modalities are intragastric balloons (IGB) and endoscopic sleeve gastroplasty (ESG). IGBs are placed into the stomach endoscopically and infused with saline to occupy space in the stomach and lead to weight loss in combination with comprehensive lifestyle interventions. There are two FDA-approved and commercially available IGBs in the US: Orbera(222) andSpatz3(223). There are other similar FDA-approved devices that are not commercially availabledue to the manufacturer's decisions. Orbera and Spatz3 are endoscopically placed and removed after the duration of the intervention is completed. Both devices are options for temporary weight loss who have a BMI of 30-40 kg/m2. A systematic review and meta-analysis were completed in 2022, looking at the effectiveness of endoscopic bariatric interventions(224) at 6 months. 10 studies reviewed IGB compared tolifestyle intervention. The pooled estimate was 6.37% total body weight loss (TBWL) at 6 months (95% CI [3.94, 8.80]). A technical review completed on IGBs by the American Gastroenterology Association (AGA) showed similar findings to the group's initial data review,with a mean weight loss of 15.62–37.60 lb. (MD, 15.46 lb.; 95% CI, 10.42–20.51 lb.) at six months and a mean weight loss of 16.2–20.68 lb. (MD, 9.76 lb.; 95% CI, 6.38– 13.14 lb.) at 12 months.(225) In this technical review safety of IGB was also evaluated. The overall rate ofserious adverse events was 5.6% (58 of 1028) in a pooled analysis including esophageal ### Page 59 mucosal injury, gastric ulcer/bleeding, severe dehydration, bowel obstruction, and aspiration pneumonia. The Orbera device is a non-adjustable IGB that is approved for 6 months of insertion in the US. The Spatz3 device is an adjustable IGB that is approved for 8 months of insertion in the US. Following FDA approval, the safety of both devices has been demonstrated for 12 months.(226,227) The Work Group felt that the benefits of having a reversible, minimallyinvasive procedure would be desirable to most patients. The weight loss with the IGB was consistent, and the procedure could be completed in the outpatient setting. The rates of adverse events prompting early removal were of concern. Consistency and evidence support short-term use of IGB with a CLI for weight loss in patients with obesity, and IGBs should be offered as part of a comprehensive program to respect provider and patient preferences. Access to IGB is limited to areas that have endoscopists with training and supplies to complete the procedure. Compared to other metabolic and bariatric procedures, IGB is technically the least challenging. IGB may provide a short-term, non- permanent option for active-duty Service members, as the IGB does not permanently alter the gastrointestinal organs and can be removed to meet operational demands. There was a higher approval amongst active-duty Service members than the VA, as IGB is the only therapy approved for use for active-duty Service members.(228-230) In the VA population, otherendoscopic therapies or surgeries are approved and demonstrate more durability. While IGBs are effective therapies for short-term weight loss, there is a concern for weight regain following removal. A recent database review in the VA showed that IGB resulted in more rapid weight loss than semaglutide (12.7 vs 9.4 kg) in 6 months following initiation of therapy. However, despite ongoing participation in CLI, the average weight regain was 3kg at 1 year (23.6% of weight lost).(231) Another study looked at intragastric balloons as an option for short-term weight management as a bridge to non-bariatric elective surgery in patients with a BMI >35. The IGB was effective at reaching goal weight loss of 14.0 kg ± 7.4 kg prior to surgery. However, at 3 months following removal, an average of 5.8kg was regained.(232) The Work Group systematically reviewed evidence related to this recommendation.(224,225)Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in the qualityof the evidence was low. The body of evidence had some limitations, including a small sample size and no long-term follow-up in US patients.(224,225) The benefits of the intragastric balloonon weight loss slightly outweigh the potential harm of adverse events, including symptoms prompting early removal. Patient values and preferences were similar because patients preferred the minimally invasive, reversible, and outpatient nature of the procedure. Thus, the Work Group decided upon a Weak For recommendation. Recommendation - 12. We suggest metabolic and bariatric surgery, in conjunction with a comprehensivelifestyle intervention, for durable weight loss in patients with a body mass index ≥30kg/m² with type 2 diabetes mellitus or with a body mass index ≥35 kg/m². ### Page 60 (Weak for | Reviewed, Amended) Discussion Metabolic/bariatric surgery (MBS), in conjunction with comprehensive lifestyle intervention, is shown to result in significant and durable weight loss. Advances in minimally invasive surgical techniques, surgical instrumentation, and quality improvement and accreditation programs have led to significant reductions in morbidity and mortality and increased public acceptance of these procedures. Despite the invasiveness of surgery and the small but real risk of significant adverse events, including those associated with gastrointestinal surgery in general, and those associated with metabolic surgery specifically, such as dumping syndrome, mineral/vitamin deficiency, decreased bone density, and postprandial hypoglycemia syndrome (NIPHS [noninsulinoma pancreatogenous hypoglycemia syndrome]).(233-235) Nonetheless, the benefitsof MBS, which include a large amount of sustained weight loss, improvement in significant metabolic comorbidities, and increased long-term survival, outweigh the potential harms. The CPG reviewed an evidence base that included a meta-analysis of randomized clinical trials comparing MBS versus lifestyle intervention (LI), medical therapy (MT), or both.(236) Asystematic review of 47 studies comparing different metabolic/bariatric operations (237), and asystematic review of 15 studies comparing MBS with non-operative weight management for the presence of fractures after weight loss (238) were also reviewed. In the meta-analysis of 21randomized clinical trials comparing MBS and LI/MT, surgery was associated with a significantly greater reduction of BMI and percent weight loss (by 6.01 kg/m2 and by 17.7%, respectively).(236) Multiple randomized studies confirm the superiority of surgical intervention over medical management without pharmacotherapy in the treatment of type 2 diabetes mellitus in individuals with Class 1 obesity (BMI 30-34.9 kg/m2). In a 2016 study of individuals with BMI >30 kg/m2,Cummings et al. (2016) showed that more than half of patients who underwent MBS had diabetes remission after 1 year, exceeding the rate of remission in the group undergoing intensive lifestyle and medical intervention, and concurrently showed superior weight loss outcomes. (239) Others demonstrated similar weight loss and diabetes control benefit, 2 and 3years after surgery in patients with a BMI >30 kg/m2.(240,241) In the 2018 study by Simonson etal. (241) that included patients with BMI >30 kg/m2 (32% of whom had BMI 30-34.9 kg/m2), 42%of the surgical cohort had diabetes remission, while 0% of the intensive lifestyle management cohort achieved this glycemic control after 3 years. Randomized trials with 5-year outcomes, published 2017-2020, demonstrated superior partial or complete remission of type 2 diabetes mellitus after MBS compared with CLI, along with superior weight loss.(242-244) A subgroup analysis of patients with BMI <35 kg/m2 by Schauer et al. (2017) showed consistent, durable weight loss and glycemic control following surgery that was superior to intensive medical therapy in this BMI range, and similar to the subgroup of BMI >35 kg/m2.(244)Furthermore, they subsequently identified unique metabolomic profiles in the surgical group.(245) Similarly, in a 2-year randomized clinical trial of 100 patients with type 2 diabetes ### Page 61 and BMI 30-35 kg/m2, Cohen et al. (2020) demonstrated a rate of remission of diabetes of 24.4% after best medical treatment, compared with 44.5% after MBS.(246) Randomized trials inAsian populations with Class 1 obesity and type 2 diabetes mellitus similarly demonstrated superior weight loss and improvement in diabetes parameters in cohorts undergoing MBS compared with usual care, after 1 and 5 years.(247,248) In the study by Cheng et al.(2022)(247), complete diabetes remission was achieved in 50% of the cohort undergoingsurgery, compared with 0% in the medical group after 12 months. After 5 years, 42% of the surgical patients remained in diabetes remission. Liang et al. (2013) found that 90% of the surgical group experienced diabetes remission after 1 year, compared with none in the non- surgical group.(248) Multiple randomized clinical trials included the population with a BMI >35 kg/m2. However, therehave been no prospective trials comparing MBS vs. CLI in the population with BMI >35 kg/m2with no other morbidity. Nonetheless, analysis of this group in available evidence suggests a clear weight loss benefit to MBS. Superior weight loss outcomes after surgery were demonstrated in the cohort with BMI >35 kg/m2 and sleep apnea after 2 and 10 years.(249,250)Similar results were also found in the population without specific obesity-related metabolic disease. In a randomized clinical trial of 80 patients with BMI >35 kg/m2 in need of total kneearthroplasty, Dowsey et al. (2022) showed that BMI reduction was significantly greater in the surgical group compared with the group receiving non-surgical treatment as usual after 12 months.(251) In a randomized trial of 20 patients with end-stage renal disease undergoingkidney transplant, with or without MBS, the patient with a BMI >35 kg/m2 who underwentsurgery had significantly greater weight loss after 1 year compared with those patients who did not have MBS.(252) In a prospective randomized trial comparing MBS with a no-surgeryprogram in a population with Class 1 obesity that included patients with a BMI of 35 kg/m2,O’Brien et al. (2013) showed significantly better weight reduction after 10-year follow-up in the surgical group.(253) And in a randomized clinical trial of 66 participants with BMI >35 kg/m2,who also had idiopathic intracranial hypertension, MBS produced weight reduction that was significantly better than community weight management with meal replacement, throughout the 2 years of the study.(254) MBS has been performed for decades and is recognized as an effective modality to produce significant and durable weight loss in individuals with severe obesity.(255) More recently, it hasalso been shown to produce lasting improvement in obesity-related comorbidity. Thus, although it involves abdominal surgery with the potential for morbidity, the risk for significant adverse events is low and deemed acceptable.(256) Patients generally seek surgical managementreflecting their values that incorporate these findings, anticipating that the desired endpoints will be achieved, and understanding that MBS is associated with improved quality of life.(237)Nonetheless, surgery is generally associated with a higher potential for morbidity than other treatment modalities and is likely a significant patient consideration when deciding whether to undergo MBS. In addition, patients experience stigma related to undergoing bariatric surgery(257,258), which may impact their decision-making. ### Page 62 Subgroup considerations are largely influenced by the large number of resources necessary to maintain a bariatric surgical program; among these are specialty surgeons with training in MBS who are not available at every VA or DOD medical center. In addition, providers with expertise in early recognition and knowledge of intervention for the potential of early weight plateau or weight regain after surgery are an important adjunct to optimal long-term outcomes. Long term, however, the durable improvement of obesity comorbidities such as diabetes leads to overall cost savings after surgery.(259) In patients who are treated with pharmacotherapy alone,studies demonstrate that significant weight regain occurs with discontinuation of these agents, so that pharmacotherapy alone would require long-term medication adherence and associated incurred costs (seeRecommendation 15). Similar recommendations have been endorsed by ajoint statement of the largest national and international organizations representing metabolic/bariatric surgeons.(260) Reports comparing long-term outcomes of surgery andpharmacotherapy with GLP-1 RAs are needed. The references cited in this section are outside the scope of the review and, therefore, did not influence the strength of the recommendation. Yet, here they provide context in support of the accumulated body of knowledge that is associated with obesity, obesity stigma, and metabolic/bariatric surgery. The Work Group systematically reviewed evidence related to this recommendation.(236-238)Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in the qualityof the evidence was low. The body of evidence had some limitations, including small sample sizes, comparator (non-operative) groups whose components were not fully defined, different kinds of operations included in the surgical groups, and a lack of blinding of participants. The benefits of weight loss after MBS, and improved glycemic control in patients with type 2 diabetes, outweigh the potential harm of gastrointestinal surgery. Patient values and preferences varied largely because some patients prefer non-invasive treatments, and stigma persists around surgery for weight loss among patients and referring providers. Thus, the Work Group decided upon a Weak For recommendation. Recommendation - 13. We suggest endoscopic sleeve gastroplasty (ESG) for weight loss, in conjunction with acomprehensive lifestyle intervention, to patients with a body mass index ≥30 kg/m². (Weak for | Reviewed, New-added) Discussion Endoscopic sleeve gastroplasty (ESG) is a minimally invasive, organ-sparing endoscopic procedure where the anterior and posterior walls of the stomach are sutured together and the length of the stomach is shortened. The overall size of the stomach is reduced by 70-80%. Currently, the FDA has approved an endoscopic suturing system specifically for ESG, the Apollo ESS System.(261) The procedure can be used as a primary modality for EBT or as arevision procedure. ESG is FDA-approved for a BMI of 30-50 kg/m2. A systematic review and meta-analysis were completed in 2022, looking at the effectiveness of endoscopic bariatric interventions(224) at 6 months. 2 studies reviewed ESG compared to ### Page 63 lifestyle intervention and showed superior weight loss at 6 months. 12-month studies showed similar effects. An additional randomized control trial with ESG and CLI was identified with 71 patients showing TBWL of 11% for ESG + CLI: 11( 95% CI = 8.86 to 13.15) vs 2.7% with CLI alone(95% CI 0.14 to 5.44).(262) In this study, there were no device-related SAEs observed.The ESG group reported that 80% (41/51) of patients had improvement in one or more metabolic comorbidities. This data is similar to other studies, which demonstrate efficacy and safety compared to comprehensive lifestyle interventions.(262) Additional studies were available that were outside the scope of the evidence review. In the endoscopic sleeve gastroplasty for treatment of Class 1 and 2 obesity (MERIT) trial, ESG was reviewed in a prospective multicenter fashion.(263) The trial looked at 209 patients (ESG=85,control=124) over the course of 52 weeks. ESG has been demonstrated to be a safe modality with pooled adverse events ranging from 1.5-2.5% in several meta-analyses and is generally regarded as having lower SAEs compared to laparoscopic sleeve gastrectomy.(264-267) SAEs associated with the procedure includenausea requiring hospitalization, bleeding, and perigastric leaks. Despite the efficacy and safety of ESG, access to the therapy is limited. The procedure is technically more challenging compared to IGB and requires an endoscopist trained in endoscopic suturing. There is limited insurance coverage of the procedure at this time, which decreases access to care for some patient populations. When compared to semaglutide, the cost-effectiveness of ESG over 5 years is favorable ($3591 vs 13,618).(268) The procedure isnot allowed in active-duty Service members as it has gastrointestinal-altering effects similar to bariatric surgeries. The Work Group systematically reviewed evidence related to this recommendation.(224,262)Therefore, it is categorized as Reviewed, New-added. The Work Group’s confidence in thequality of the evidence was very low. The body of evidence had some limitations, including small sample sizes and a lack of study data longer than 2 years. The benefits of ESG were having a minimally invasive, organ-sparing procedure with no difference in SAEs compared to CLI and improved QoL outcomes. These benefits outweighed the potential harm of device failure or preclusion of other bariatric procedures. Patient values and preferences were similar because of the minimally invasive nature of the procedure. Thus, the Work Group decided upon a Weak for recommendation. Introduction to the 2025 OBE CPG Pharmacotherapy Recommendations:Pharmacotherapy should be used in conjunction with CLI for weight loss for individuals with aBMI ≥30 kg/m2 or BMI ≥27 kg/m2 with an obesity-associated condition, as this was the patient population represented in the evidence base. All clinical trials of pharmacotherapy were conducted in conjunction with a CLI, and study medication was generally administered concurrently. Therefore, the Work Group specified the importance of initiating pharmacotherapy in conjunction with a CLI in the recommendation. However, the Work Group did not identify evidence to guide decisions for when to initiate pharmacotherapy in conjunction with CLI. ### Page 64 Providers should acknowledge and respect patients' decisions regarding pharmacotherapy. This involves ensuring that patients are well-informed about their treatment options, including the risks, benefits, and potential alternatives, and that their decisions are made voluntarily and without coercion. For the purposes of this document, we have deliberately and consistently used the term“Obesity Medications” for medical clarity. This reflects the use of these medications in healthcare settings to address the disease of obesity. “Weight Management Medications,”however, is the preferred terminology for patient-centered communication and public health messaging to avoid stigmatizing language. Clinical Care Notes: When managing patients with diabetes mellitus who are taking anti- glycemic medications (most notably sulfonylureas, meglitinides, or insulin therapy), patient education and close glucose monitoring are appropriate at the start of any weight loss intervention, including diet and exercise, to decrease the risk of hypoglycemia. When adding pharmacotherapy agents, such as NuSH /GLP-1 RA agonist-containing agents, dose reduction of other diabetes medications that cause hypoglycemia, such as insulin therapy, may be warranted. Avoiding hypoglycemia events is important. Excess basal insulin dosing (e.g, glargine insulin) can also hinder weight loss efforts as hypoglycemia, especially nocturnal hypoglycemia, will trigger the release of counterregulatory hormones that will stimulate appetite and insulin resistance. It is not recommended to combine Dipeptidyl peptidase 4 inhibitors (DPP4i) therapy with NuSH /GLP-1 RA agonist-containing agents, as this combination does not provide additive glucose-lowering effects. Recommendation - 14. There is insufficient evidence to recommend either for or against delaying the start of pharmacotherapy, in relationship to CLI, to improve outcomes in patients with overweight or obesity. (Neither for nor against | Reviewed, New-added) Discussion Many clinical guidelines(9,269) recommend a 6-month course of comprehensive lifestyleintervention (CLI) before initiating pharmacotherapy for overweight and obesity. Landmark trials such as the Diabetes Prevention Program and Look AHEAD report average weight losses of 5–10% at one year with CLI, versus 1–2% in control groups.(270,271) While 55–65% of participantsachieve ≥5% weight loss, and 10–15% lose ≥15%, 35–50% do not reach the clinically meaningful 5% threshold.(9,272,273) Weight loss often plateaus by 6–9 months, and most individuals regainabout one-third of their lost weight within a year, with further regain over time.(117,274)Maintenance strategies like monthly counseling can slow regain, though some regain occurs in the majority of individuals. CLI is the pillar of any weight management strategy, but often metabolic adaptations that favor weight regain will cause individuals to regain weight despite their best efforts.(16,17) A stepped-care model, in which patients initiate treatment with CLI and escalate to pharmacotherapy or surgery based on response, may pose several limitations. Patients face ### Page 65 practical barriers, logistical, financial, and social, that impede participation in intensive programs, and access to intensive CLI often remains limited, especially in primary care, with most programs concentrated in academic or commercial settings.(275) While the VA MOVE! program is availableto all Veterans receiving care in VHA, the Military Health System (MHS) often lacks the staff and infrastructure to provide comparable services. Feedback from Veterans, dependents, and active- duty personnel from the Patient Focus Group highlights inconsistent content and specificity of CLI messaging, reducing its effectiveness. Requiring CLI as a prerequisite to pharmacologic therapy may inadvertently reinforce weight stigma by attributing treatment failure to personal shortcomings rather than recognizing the complex neurobiological and physiological mechanisms underlying obesity. The Patient Focus Group conducted for this CPG expressed frustration with being required to participate in specific CLI programs before accessing obesity medications, particularly after experiencing repeated difficulty achieving sustainable weight loss through prior individual or structured lifestyle interventions. Phase 3 trial data evaluating semaglutide and tirzepatide demonstrate that adding intensive behavioral therapy or lifestyle intervention provides minimal additional weight loss beyond what is achieved with pharmacotherapy alone.(276-279) Both agents also led to significant improvementsin hypertension, lipid profiles, and other metabolic parameters compared to placebo, highlighting their potential to deliver substantial health benefits beyond weight reduction. While these findings stem from indirect comparisons, the results support a potential shift toward earlier, individualized pharmacologic treatment, particularly for patients with obesity-related comorbidities. Given the above information, the Work Group aimed to evaluate the optimal timing for the initiation of pharmacotherapy for obesity medications, whether that was alongside CLI or after a period of CLI. However, our systematic search identified no studies that directly addressed this question. To date, no randomized controlled trials have directly compared outcomes of initiating pharmacotherapy after a period of CLI versus starting pharmacotherapy concurrently with CLI, particularly in patients with obesity-related comorbidities. For individuals with more severe obesity- related comorbidities (i.e., Stage 3-4), early initiation of obesity medications may lead to better outcomes. Requiring a course of CLI before prescribing pharmacotherapy may delay weight loss, contribute to patient frustration, and reduce engagement in care. Alternatively, initiating a course of CLI prior to pharmacotherapy may offer benefits, particularly for individuals without severe obesity-related comorbidities, those not yet prepared to initiate pharmacologic treatment, or in whom pharmacotherapy is contraindicated. Given the challenges of maintaining weight loss with CLI alone and the high risk of weight regain due to physiological adaptations(16,17), it is critical toidentify optimal time points for intensifying treatment with pharmacotherapy and bariatric surgery. Proactive discussions about pharmacologic or surgical options, even when patients are making progress with lifestyle efforts, can support shared decision-making and improve long-term weight loss and weight maintenance success. While a network meta-analysis would be needed to determine the ideal timing of medication initiation relative to other weight loss interventions, adopting a more flexible, individualized approach that prioritizes timely access to effective therapies is both reasonable and supported by emerging evidence. ### Page 66 With the advent of newer and more effective obesity medications, there is growing support for earlier use of obesity medications, particularly in patients with more severe obesity and/or obesity- related comorbidities. Rather than serving as a prerequisite, clinical practice experts (275,280-285) are starting to discuss the importance of CLI as a necessary complement to pharmacologictherapy to ensure nutritional adequacy, preserve lean mass and physical function, and reduce the risk of sarcopenia and micronutrient deficiencies during weight loss. The Work Group systematically reviewed the evidence on the optimal timing of pharmacotherapy in relation to CLI; however, no studies meeting the inclusion criteria were identified. Therefore, it is categorized as Reviewed, New-added. The Work Group’s confidence in the quality of theevidence was not applicable, as there was no evidence pulled. Thus, the Work Group decided upon a Neither for nor against recommendation. Recommendation - 15. We suggest against discontinuing obesity medications, taking into account patient characteristics and preferences, as it results in weight regain. (Weak against | Reviewed, New-added) Discussion Substantial weight regain occurs after discontinuation of weight loss pharmacotherapy. Two RCTs [SURMOUNT 4, Aronne et al. (2024) (279), and STEP 4 Rubino et al. (2021) (286)] comparedcontinuation of tirzepatide or semaglutide to discontinuation of these medications with a placebo control, after 36 or 20 weeks of initial therapy, respectively. In both studies, on nearly all measures, including body weight, waist circumference, laboratory markers of glucose and lipid metabolism, as well as mental health and quality of life outcomes, continuation of the medication was superior to discontinuation. In STEP 4(286) after 20 weeks, switching to placebo resulted in+6.9% mean body weight gain compared to -7.9% mean body weight loss with continuing semaglutide from 20-68 weeks (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). In SURMOUNT 4, the mean percent weight change from week 36 to week 88 was −5.5%with continued tirzepatide vs +14.0% with switch to placebo (difference, −19.4% [95% CI, −21.2% to −17.7%]; P < .001)There was no difference in the frequency of serious adverse events between the continuation arm vs. the placebo arm. The evidence in both studies is of high quality, with double blinding, randomization, and allocation concealment procedures clearly defined. Each had over 200 patients per arm, allowing for sufficient power. A noteworthy limitation is that both SURMOUNT 4 Aronne et al. (2024). (279) and STEP 4 Rubino et al. (2021) (286), selected tocompare only those patients who had tolerated up-titration to maximally tolerated doses of the agent, which may lead to an overestimation of benefit when applied to a more general population. Though not specifically designed to compare the effect of discontinuation after weight loss, in SURMOUNT 1 Jastreboff et al. (2024) (287) RCT comparing tirzepatide vs. placebo, after theinitial 176-week study period, participants were followed for an additional 17 weeks off-treatment period. Weight regain occurred during the 17-week off-treatment period after tirzepatide discontinuation. ### Page 67 There is some variation in patient preference, with some patients preferring to continue with an agent that has created effective weight loss, and others who would discontinue due to polypharmacy or concern for potentially unknown long-term risks of use, or intolerance. Some patients may potentially choose to continue on medications for secondary benefits on other comorbidities (e.g., OSA, CKD, CVD, heart failure), though data remains unclear whether these additional benefits are still achieved in the absence of weight loss. Resource use for long-term therapy is also an important consideration that requires further evaluation in the context of both resource scarcity as well as QALY (quality adjusted life year) gained, and morbidity avoided, from maintained weight loss. Note that data is lacking for the weight effects of gradual de-escalation prior to discontinuation of pharmacotherapy for weight loss. Please seeRecommendation 16 below. An additional study that was not in the evidence base, STEP 1 Wilding et al. (2022)(288), alsofound that one year after the withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss. The Work Group systematically reviewed evidence related to this recommendation (279,286,287). Therefore, it is categorized as Reviewed, New-added. The Work Group’sconfidence in the quality of the evidence was high. The harms and burdens of weight regain that ensue from discontinuing obesity medications outweigh the benefits of discontinuing obesity medications. However, patient values and preferences varied because some patients prefer not to be on a long-term medication for weight loss, and resource use remains a concern. Longer- term studies >4 years are needed to determine whether weight regain also results when obesity medications are discontinued after a longer period of use. Thus, the Work Group decided upon a Weak against recommendation. Recommendation - 16. There is insufficient evidence to recommend either for or against reduction of the dose or frequency of pharmacotherapy to maintain achieved weight loss and avoid weight regain. (Neither for nor against | Reviewed, New-added) Discussion Patients and providers are eager to know, once weight targets are met with an obesity medication, does reducing the dose or the frequency of the medication permit maintenance over time? What happens to additional measures of health after dose or frequency reduction of obesity medications? The Work Group dedicated a Key Question to attempt to answer this specific question. However, in reviewing the literature published on or after April 1, 2019, to January 6, 2025, the only data available compared continuation at the highest dose tolerated vs. complete discontinuation of the obesity medication. The data suggest that substantial weight regain occurs after complete discontinuation of weight loss pharmacotherapy (seeRecommendation 15 for amore thorough discussion in this regard. Briefly, the Work Group suggests against discontinuing obesity medications as it results in weight regain. No studies were found that evaluated reducing the dose or frequency of a medication initiated for weight loss and using a lower maintenance dose or frequency of dosing to maintain weight loss. Therefore, given the lack of data, we are ### Page 68 unable to make a recommendation in this regard. This highlights the need for future research regarding weight management pharmacotherapy dosing and frequency options. The Work Group recognizes that there is a large variation in patient perspectives regarding long- term obesity medication use. Some patients do not want to be on any medications, while others prioritize maintaining the weight loss achieved, so they would prefer to continue at a reduced dose or frequency if able to maintain the weight loss achieved. The potential harms from dose or frequency reduction of obesity medications include the risk of weight regain and subsequent complications of obesity. There is an ongoing cost associated with ongoing medical management, as well as risks of side effects. In the absence of data, individualization of therapy is necessary for each patient based on their preferences, values, and goals. Patients who are actively losing weight will benefit from clinical monitoring to assess whether other medications, such as antihypertensives and anti-glycemic agents, require de-escalation or discontinuation. Close monitoring and continued engagement in lifestyle and behavioral weight management resources may be beneficial to support weight maintenance if pharmacotherapy is de-escalated.(289)Patients who do not respond to weight loss medications should be engaged in discussion to identify possible factors such as adherence, negative emotions with weight loss leading to anxiety and depression. The Work Group systematically reviewed evidence related to this recommendation, and no studies from April 1, 2019, to January 6, 2025, were found to meet the inclusion criteria to determine whether reducing the dose or frequency of pharmacotherapy maintains achieved weight loss and avoids weight regain. Therefore, it is categorized as Reviewed, New-Added. With no studies to assess, the Work Group is unable to make any statement on confidence in the quality of the evidence. Patient values and preferences vary largely because some patients prefer to discontinue pharmacologic agents, while others would prioritize maintaining the weight loss achieved and remaining on an obesity medication that is effective for them long-term. Thus, the Work Group decided upon a Neither for nor against recommendation. Recommendation - 17. We recommend semaglutide or tirzepatide for both weight loss and to maintain weight loss, in conjunction with a comprehensive lifestyle intervention, in patients with a bodymass index ≥27 kg/m2 who also have an obesity-associated condition; and those whohave a body mass index ≥30 kg/m2. (Strong for | Reviewed, New-added) Discussion Pharmacotherapy should be used in conjunction with CLI for weight loss for individuals with a BMI≥27 kg/m2 with an obesity-associated condition or BMI ≥30 kg/m2, as this was the patient population represented in the evidence base. All included clinical trials of pharmacotherapy were conducted in conjunction with a CLI, and study medication was generally administered concurrently. Therefore, the Work Group specified the importance of initiating pharmacotherapy in conjunction with a CLI in the recommendation. ### Page 69 The overall confidence in the quality of the evidence was determined to be moderate. Semaglutide and tirzepatide had a clinically and statistically significant benefit over placebo in the critical outcome of percent change in relative body weight. For semaglutide, a network meta- analysis (NMA) by Dorneles et al. (2024) (290) included studies with follow-up ranging from 24 to104 weeks. The average percent change in relative body weight was -11.8% compared to placebo, demonstrating semaglutide’s efficacy in both weight loss and maintaining weight loss.For tirzepatide, an NMA by Liu et al. (2024)(291) included studies with follow-up ranging from 72to 88 weeks. The average percent change in relative body weight from the included studies ranged from -15% to -21.2%, depending on the maintenance dose of tirzepatide used. A higher percent change in relative body weight appeared to be associated with higher doses. FDA- approved maintenance doses for tirzepatide are 5mg, 10mg, and 15mg weekly. A longer, 176- week, follow-up is reported in an article by Jastreboff et al. (2024)(287) in patients with obesityand prediabetes, with an average percent change in relative body weight of -11.1%, -17.5%, and - 18.4% for tirzepatide 5mg, 10mg, and 15mg weekly, respectively, versus placebo. Thisdemonstrates tirzepatide’s efficacy in maintaining weight loss. A study by Knop et al. (2023)(292) demonstrated significant weight loss (average -12.7% relativebody weight change) at 68 weeks with oral semaglutide 50mg daily versus placebo. It should be noted that semaglutide is not currently commercially available in 50mg tablets, nor is a 50mg dose achievable in the currently commercially available oral tablets of semaglutide (RYBELSUS®). The FDA is currently evaluating the application for oral semaglutide 25mg daily for the treatment of overweight and obesity based on results from the OASIS 4 trial (article not published at the time of CPG publication, NCT05564117). Oral semaglutide has also not had evidence to support the other health benefits that subcutaneous semaglutide has for people with overweight and obesity (discussed later in this narrative). The Knop et al. (2023) study supports the efficacy potential for oral semaglutide in weight loss. The Work Group determined that the benefits for weight loss and maintenance of weight loss slightly outweighed the harms and burdens. For all the included evidence(287,290,291), there wasno significant increase in serious adverse events for semaglutide or tirzepatide versus placebo.The most common (≥ 10% reported incidence) side effects of both semaglutide and tirzepatideare GI intolerances, including nausea, vomiting, diarrhea, constipation, and abdominal pain.(293,294) The provision of CLI in conjunction with these medications may help improve GItolerance as well as prevent nutritional deficiencies (e.g., muscle and bone loss).(295) Bothmedications have boxed warnings contraindicating use in people with a personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia Syndrome Type 2. Other warnings include risk of acute pancreatitis, gallbladder disease, acute kidney injury, hypoglycemia, and, in people with type 2 diabetes, diabetic retinopathy. Because of the potential for fetal harm, it is recommended that semaglutide be discontinued in females and males at least 2 months before they plan pregnancy. Tirzepatide is also not recommended for use during pregnancy, and in addition, there are cautions that oral hormonal contraceptive efficacy may be decreased by tirzepatide. It is recommended that patients using oral hormonal contraceptives switch to a non- oral contraceptive method or add a barrier method of contraception for four weeks after initiation and any dose increases of tirzepatide. There have been rare post-marketing reports of pulmonary aspiration in patients taking GLP-1 agonists who are undergoing general anesthesia or deep ### Page 70 sedation. Suicide behavior and ideation continue to be warnings on the prescribing information of both tirzepatide and semaglutide, though recent evidence suggests that there may not be an associated risk with this class of medications.(296) There are many subgroups of patients with overweight and obesity that may have the potential for additional health benefits from semaglutide or tirzepatide. Some of these studies were outside the evidence review but noted here as potential reasons a provider may choose semaglutide or tirzepatide as an opportunity to treat overweight/obesity and another condition. Both semaglutide and tirzepatide have evidence to improve HbA1c in people who have diabetes(297,298), reducethe new onset of type 2 diabetes(287), and improve symptoms with heart failure with preservedejection fraction(299,300). The SELECT trial(301) demonstrated that people with overweight orobesity and cardiovascular disease (defined as prior myocardial infarction; prior ischemic or hemorrhagic stroke; or symptomatic peripheral arterial disease with an ankle-brachial index < 0.85, peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease) had a 20% decreased risk of secondary cardiovascular events with semaglutide versus placebo. The SURMOUNT-OSA(302) trial demonstrated an improved apnea-hypopnea index withtirzepatide versus placebo in people with obesity and moderate to severe obstructive sleep apnea. As once-weekly injected medications, some patients may prefer semaglutide or tirzepatide because of their less frequent administration than a daily medication. On the other hand, some patients may prefer oral medications over injected ones. Both semaglutide and tirzepatide should be stored in refrigeration, which may present a challenge for some subgroups who do not have access to refrigeration for their medications. Both semaglutide and tirzepatide are only available as branded medication (i.e., no generic is currently available), which may make them cost- prohibitive to some patients and/or healthcare systems. Obesity medications are also something that needs to be taken long-term, if not lifelong, as current evidence supports that weight regain occurs when the medication is discontinued (seeRecommendation 15). A cohort study by Rodriguez et al. (2025)(303) found that most patients with type 2 diabetes hadhigher rates of discontinuation and lower rates of reinitiation of GLP-1 therapy, compared to patients with overweight and obesity without type 2 diabetes in a one-year time frame. It is important to consider patient-specific factors and monitor for adverse effects in the titration of these agents for optimal tolerance and weight management success. The Work Group systematically reviewed evidence related to this recommendation.(287,290,291)Therefore, it is categorized as Reviewed, New-added. The Work Group’s confidence in the qualityof the evidence was moderate. The body of evidence had some limitations, including inconsistency of results, which may have been a function of NMAs that included a variety of studies with different inclusion and exclusion criteria for their participants. The benefits of weight loss and maintenance of weight loss slightly outweigh the potential harms of adverse event risk. Patient values and preferences varied somewhat because of the route of administration, dosing frequency, and duration of treatment to maintain weight loss. Thus, the Work Group decided upon a Strong for recommendation. ### Page 71 Recommendation - 18. We suggest phentermine/topiramate extended release (ER) or liraglutide for both weight loss and to maintain weight loss, in conjunction with a comprehensive lifestyle intervention,in patients with a body mass index ≥27 kg/m2 who also have an obesity-associated condition; and, those who have a body mass index ≥30 kg/m2. (Weak for | Reviewed, New-added) Discussion The critical outcomes of a decrease in body weight and an increased number of participants with≥5%, ≥10% and >15% body weight reduction compared to lifestyle intervention were evaluated in several studies. For liraglutide, two studies were found in the literature search. There was evidence from 4 RCTs in 1 SR(304) that liraglutide + CLI reduced both body weight and proportion of participantsachieving >5% and >10% weight loss compared to placebo + CLI during a follow-up duration of 52 to 160 weeks with a moderate quality of evidence. In Wadden et al. (2019), liraglutide plus intensive behavioral therapy (IBT) reduced body weight, BMI, and proportion of participants achieving > 5%, > 10% and > 15% weight loss compared to placebo + CLI during a follow-up duration of 24 to 52 weeks. The quality of evidence was found to be low due to a small sample size. For phentermine/topiramate ER, one study was found in the literature search. Evidence from 5 RCTs in 1 SR,(305) phentermine/topiramate ER reduced body weight and found a higherproportion of participants achieving >5% and >10% weight loss compared to lifestyle intervention during a follow-up duration of 24 to 52 weeks with moderate to high quality of evidence. Additionally, the critical outcome of weight loss was evaluated with respect to liraglutide and phentermine-topiramate ER, which were reviewed in the 2020 VA/DOD Obesity CPG. The critical outcome of weight loss was evaluated in a large, comprehensive SR and meta-analysis (306) thatincluded 28 RCTs. The combination of a CLI and either liraglutide or fixed-combination phentermine-topiramate ER resulted in greater weight reduction than a CLI alone, with moderate confidence in the quality of the evidence. The meta-analysis reported that after a minimum follow- up of 12 months, both medications were associated with a greater reduction in total body weight compared to placebo. Further, a greater proportion of patients in the medication group achieved at least 5% or 10% weight loss from baseline compared to placebo, which is considered to be clinically significant. Another study reviewed in the 2020 CPG, in le Roux et al. (2017),(307)liraglutide + CLI led to greater weight loss than CLI alone at 160 weeks. Although liraglutide has been found to be effective for clinically significant weight loss, and no head-to-head clinical trials are included in the data analyzed, the average weight loss with liraglutide is consistently less than that seen with tirzepatide and semaglutide. In the Shi et al 2024 meta-analysis, the average weight loss with liraglutide was 4.67%, whereas with semaglutide, 11.4% weight loss was seen. In the Khera et al. (2016) (306) systematic review and meta-analysis, which did not include semaglutide or tirzepatide, patients who received fixed- combination phentermine/topiramate ER had the highest probability of achieving a 5% or 10% ### Page 72 weight loss, followed by liraglutide. Although liraglutide is recommended for weight loss and to maintain weight loss, one might consider a more efficacious medication if given a choice. Patients who do not achieve their weight loss goal with liraglutide should be transitioned to other weight loss pharmacotherapy with proven benefit to provide 7-10% weight loss (for example, in patients with MASH). Importantly, for both liraglutide and phentermine/topiramate ER in multiple studies, there were no significant differences in adverse effects reported with liraglutide or phentermine-topiramate ER compared with CLI alone.(304,305,308) We suggest both liraglutide and phentermine-topiramate ER for weight maintenance after initial weight loss. Evidence from 4 RCTs in 1 SR(304), Liraglutide + CLI reduced both body weight andproportion of participants achieving >5% and >10% weight loss compared to placebo + CLI during a follow-up duration of 160 weeks, with moderate quality of evidence. As the weight loss was maintained for 160 weeks, we recommend liraglutide for weight maintenance in addition to weight loss. The quality of this data was low, thus we could only assign a Weak for recommendation. One systematic review (115) and one RCT (307) reviewed in the 2020 VA/DOD Obesity CPG alsodemonstrated a benefit on maintenance of weight loss with liraglutide. LeBlanc et al. (2018) (115)demonstrated a maintenance of 5% or 10% weight loss during 13 months of follow-up (after an initial weight loss of at least 5%), favored treatment with liraglutide compared to placebo. In le Roux et al. (2017),(307) liraglutide induced greater weight loss than placebo at week 160. The 2014 VA/DOD Obesity CPG included high certainty evidence in support of the role of fixed- combination phentermine/topiramate ER in maintenance of weight loss. Garvey et al. (2012) (309)found that significantly more patients in the fixed-combination phentermine/topiramate ERtreatment groups experienced a ≥5% weight loss (79.3% with fixed-combinationphentermine/topiramate 15 mg/92 mg versus 30% with placebo) or ≥10% weight loss (53.9% with fixed-combination phentermine/topiramate 15 mg/92 mg versus 11.5% with placebo) after 108 weeks. This leads us to continue to recommend phentermine-topiramate ER to maintain weight loss. Unlike newer NuSHes/GLP-1 RA containing agents, liraglutide is a once-daily injection compared to once weekly. Some patients may prefer the routine of using an injection daily, whereas this medication may be less desirable to patients who prefer a weekly injection. Given the shorter half- life of liraglutide, it will metabolize more rapidly should significant side effects develop, and dose titration is more rapid. Like all NuSHes/GLP-1 RA-containing agents, the most common reported side effects are GI distress, including nausea, vomiting, and diarrhea. All GLP-1 receptor agonists are recommended to remain refrigerated before use. As of this writing, liraglutide is currently the only GLP-1 agonist available as a generic medication, which may make it more affordable in the future. Liraglutide was noted to reduce the risk of major adverse cardiovascular events, including MI, stroke, and CV death, in adults with type 2 diabetes in the LEADER trial.(310) Liraglutide wasalso shown to reduce the AHI in patients with obesity.(311) As a once daily oral pill, phentermine-topiramate ER may be preferred by those who either want to avoid agents that require injection, or to minimize pill burden or frequency of medication administration per day. It comes in multiple different doses, so the dosing can be titrated to the ### Page 73 individual patient based on effectiveness and tolerability. The topiramate component may be helpful in patients who have alternative uses for topiramate, such as migraine headaches or restless leg syndrome. The Work Group systematically reviewed evidence related to this recommendation(304,305)identified through the systematic evidence review and considered evidence put forth in the 2014 VA/DOD Obesity CPG(309) and 2020 VA/DOD Obesity CPG.(115,306,307) Therefore, it iscategorized as Reviewed, Amended. The Work Group’s confidence in the quality of the evidencewas low. The body of evidence had some limitations, including a small sample size and confounders in the analysis. The benefits of both greater weight loss and maintenance of weight loss with pharmacotherapy in conjunction with CLI, compared to CLI alone, outweighed the potential harms of adverse events. Patient values and preferences varied somewhat because some patients prefer daily oral medications, whereas others may prefer less frequent dosing or opt for no medications. Thus, the Work Group decided upon a Weak for recommendation. Recommendation - 19. We suggest naltrexone/bupropion extended release (ER) for weight loss, in conjunction with a comprehensive lifestyle intervention, in patients with a body mass index ≥27 kg/m2who also have an obesity-associated condition; and those who have a body mass index≥30 kg/m2. (Weak for | Reviewed, New-added) Discussion Evidence from 1 SR and 6 RCTs(305) suggests that naltrexone/bupropion ER did not lead to aclinically important difference in percent bodyweight change compared to lifestyle intervention at 24 to 52 weeks follow-up. (SOE: Moderate). However, naltrexone/bupropion did lead to a clinically important increase in the percentage of participants with body weight reduction ≥5% or ≥10% compared to lifestyle intervention at 24 to 52 weeks follow-up (SOE: High).(305) As the maintenance dose of naltrexone/bupropion (ER) is 2 tablets twice daily, pill burden and adherence can be a concern for patients. Additionally, adjustments are needed in patients with renal and hepatic impairment; the medication must be held before sedation, and patients on chronic opiates should not use it concurrently. However, naltrexone/bupropion ER can be beneficial in the concurrent treatment of smoking cessation, alcohol use disorder, and depression. Oral formulation of the medication (as opposed to an injection) allows for ease of use and storage. Naltrexone/bupropion ER’s common adverse side effects include headache, sleep disorder, nausea, constipation, diarrhea, vomiting, dizziness, and xerostomia. Use of the medication is contraindicated with concurrent opioid use, pregnancy, uncontrolled hypertension, seizure disorder, bulimia or anorexia nervosa, abrupt discontinuation of alcohol, acute opioid withdrawal, and concurrent use of MAOI, linezolid, or IV methylene blue. Significant warnings to consider include suicidal thinking/behavior (black box warning). Neuropsychiatric symptoms may precipitate acute opioid withdrawal in patients receiving opioids, increased blood pressure ### Page 74 and heart rate, hepatotoxicity, and hypoglycemia requiring adjustments to antihyperglycemic medications (See Appendix J). The critical outcomes of weight loss and safety were evaluated in one large, comprehensive SR and meta-analysis that included 28 RCTs (n=29,018).(306) This contributed to moderateconfidence in the quality of the evidence that the combination of a CLI and an obesity medication, approved by the FDA for long-term use, including naltrexone/bupropion ER, results in greater weight reduction than a CLI alone. The meta-analysis reported that after a minimum follow-up of 12 months, naltrexone/bupropion ER was associated with a greater reduction in total body weight compared to placebo. Further, a greater proportion of patients in the medication group achieved at least 5% or 10% weight loss from baseline compared to placebo, which is considered to be clinically significant.(306) The longest duration of therapy fornaltrexone/bupropion ER for weight loss is currently 52 weeks. As the workgroup considered a minimum duration of therapy of 2 years required to make a statement regarding medication use for maintenance therapy, no statement could be made regarding the use of naltrexone/bupropion ER for weight maintenance. A meta-analysis by Shi et al. (2024)(305), found naltrexone/bupropion and phentermine had thehighest risks of adverse effects leading to discontinuation. Naltrexone/bupropion ER had less weight loss overall when compared to phentermine-topiramate; however, more participants taking naltrexone-bupropion ER achieved >5% and >10% bodyweight reduction when compared with liraglutide.(305,306) Pharmacotherapy may produce significant weight loss in conjunction with CLI; however, treatment individualization is critically important due to the potential for adverse effects. As reported in the SR by Khera et al. (2016), all of the obesity medications evaluated were associated with a statistically significant risk of medication discontinuation due to adverse events when compared to placebo.(306). Naltrexone/bupropion ER had the second-highestodds of treatment discontinuation when compared with liraglutide, phentermine/topiramate, and orlistat. (seeTable J-2)(305,306) As noted in the 2018 USPSTF systematic review(115), trials ofobesity medications often had very selective inclusion and exclusion criteria. Patients who volunteer for participation in research may have higher levels of adherence than community- dwelling patients. Patients may be excluded from participation due to medical conditions that are often present in the patient populations intended for management by this CPG. The Work Group considered the applicability of these results to the general patient population as well as the potential harms from the obesity medications. Naltrexone/bupropion ER may be specifically inappropriate for patients with conditions such as HTN, seizure disorder, drug misuse disorder potential, pregnancy, or who are breastfeeding. Patients should be informed of the risks and adverse effects of each medication to properly incorporate patient preference in the medication selection (seeAppendix J for additional information on pharmacotherapy considerations). Most studies, including the SR (312), documented the serious limitation of attrition above 30%.The benefits of naltrexone/bupropion (ER) outweigh potential patient harms when the medication regimen selected is customized to individual patients and considers comorbidities, potential contraindications, and adverse effects of the medication. Additional data should help ### Page 75 determine the long-term outcome benefit of specific pharmacotherapy as well as any potential harms with long-term maintenance. Obesity medications also have the potential for high cost and resource use with long-term therapy. In addition, as noted above, the high attrition rates in clinical trials and the SRs suggest low feasibility for long-term use. Participants in the patient focus group were interested in pharmacologic therapy for weight loss and in obtaining additional information on the efficacy as well as potential side effects of these medications (see[AppendixJ](https://performixconsulting.sharepoint.com/sites/VADoDCPGTeam/Shared%20Documents/General/08%20-%20Obesity%20Overweight%20CPG%20-%20Aug%202024/09%20-%20CPG%20Draft%203/HYPERLINK#Appendix_I_Pharmacotherapy)on pharmacotherapy and[Sidebar 2](https://performixconsulting.sharepoint.com/sites/VADoDCPGTeam/Shared%20Documents/General/08%20-%20Obesity%20Overweight%20CPG%20-%20Aug%202024/09%20-%20CPG%20Draft%203/HYPERLINK#Sidebar_2)on select medications and their potential effects onweight). The Work Group systematically reviewed evidence related to this recommendation(115,306,307,309,312-318) and considered the evidence extracted in the 2020and the current 2025 CPGs.(309,319,320) The Work Group's confidence in the quality ofevidence was moderate. The body of evidence had high attrition, which was considered a serious limitation. The benefit of greater weight loss with pharmacotherapy in conjunction with CLI compared to CLI alone outweighed the potential harms of adverse events, which may be reduced if medication selection is individualized for the patient. The lack of outcome data for long-term benefits and harms, limited feasibility due to high attrition, and higher cost and resource use compared to CLI alone were also noted. Patient values and preferences were somewhat varied. Thus, the Work Group decided upon a Weak for recommendation. Research is needed to address the numerous knowledge gaps in pharmacotherapy for weight loss and weight maintenance (seeKnowledge Gaps and Recommended Research for moreinformation). Recommendation - 20. We suggest the use of glucagon-like peptide type 1 agonist-containing agents, in conjunction with CLI, for the treatment of patients with overweight and obesity, with either co-occurring prediabetes or type 2 diabetes mellitus. (Weak for | Reviewed, New-added) Discussion Our Work Group reviewed the available evidence to determine how co-occurring obesity-related medical conditions impact the safety and effectiveness of treatments for overweight and obesity. Evidence to answer this question was limited and primarily focused on the use of glucagon-like peptide type 1 agonists and polyagonists (including a combination of Glucose-Dependent Insulinotropic Polypeptide (GIP), glucagon, and others) for weight loss in patients with and without diabetes. A network meta-analysis of 27 RCTs demonstrated significantly greater weight loss in patients with diabetes treated with NuSHes/GLP-1RA containing agents (tirzepatide, retatrutide* * Not FDA-approved at time of publication, semaglutide, liraglutide) versus placebo; however, retatrutide, semaglutide, and tirzepatide all showed significantly greater weight loss among patients without T2DM compared to patients with T2DM.(321) The confidence in the quality of the evidence was low due toindirect cross-trial comparisons between subgroups. GLP-1RAs also led to improvements in ### Page 76 waist circumference with a similar pattern of significantly greater reductions in waist circumference among patients without T2DM compared to patients with T2DM for retatrutide, semaglutide, and tirzepatide. There were no differences in severe adverse outcomes (cardiovascular events, severe gastrointestinal reactions, or infections) in those with and without diabetes. A meta-analysis of 46 RCTs comparing GLP-1 agonist containing agents (semaglutide, dulaglutide, danuglipron*, efpeglenatide*, exenatide, liraglutide, orforglipron*) showed greater reductions in Hemoglobin A1c and fasting plasma glucose for patients with diabetes (-0.90%, -1.32 mmol/L) and pre-diabetes (-0.44%, -0.71 mmol/L) compared to those without diabetes (-0.23%, -0.35 mmol/L).(322) One post-hoc RCT analysis of semaglutide usein patients with Metabolic Dysfunction-Associated Steatotic Liver Disease/Metabolic Dysfunction-Associated Steatohepatitis (MASLD/MASH) also showed significant weight loss in patients with pre-T2DM and T2DM compared to placebo.(323) Our evidence review also returned a post hoc analysis of an RCT investigating the use of Intensive Lifestyle Intervention (ILI) in patients with T2DM, but the study did not include a comparison group without diabetes.(324) A meta-analysis of 14 RCTs examining theeffectiveness of ketogenic diets in those with and without T2DM did not include the critical outcome of weight loss and thus did not contribute to our recommendation.(158) We did notretrieve any studies that compared treatments in patients with and without ASCVD, heart failure, or MASLD/MASH. Additional studies were retrieved from other key questions in our evidence review that support the use of GLP-1RAs in a variety of co-occurring obesity related conditions; however, they lack direct comparisons of patients with and without the conditions. This limits our ability to answer how a given condition impacts the safety and effectiveness of the intervention. For example, the SURMOUNT-4 trial showed sustained weight loss at 88 weeks with tirzepatide in a variety of obesity-related conditions, such as ASCVD and MASLD, but outcomes were not compared among subgroups.(279) In addition, RCTs such as SUSTAIN-6, PIONEER-6, andSOUL have demonstrated the cardiovascular benefits of semaglutide (in both injection and oral formulations) for T2DM; however, these studies were not included in our evidence review because they were not limited to patients with overweight and obesity, which is the focus of this guideline. As such, we are not able to make specific recommendations on how co-occurring ASCVD impacts the safety and effectiveness of treatments for overweight and obesity.(325-327)The evidence review highlights the difficulty of assessing the complex interplay of multiple comorbidities typically seen in clinical practice. Our review of the evidence demonstrated multiple benefits of NuSHes/GLP-1 RA-containing agents for patients with obesity/overweight and T2DM, including weight loss, decreased abdominal circumference, and improved glycemic control. Improved glycemic control also extended to patients with prediabetes. In clinical practice, we have also observed the benefit of being able to wean other obesogenic medications, such as insulin and sulfonylureas, by using GLP-1 RAs. Notably, there was no significant difference in serious adverse events compared to placebo. However, we acknowledge that side effects are common and can lead to discontinuation of therapy in clinical practice. Overall, we find that the potential benefits of GLP- 1 RA therapy outweigh the risk of harms in diabetes mellitus and prediabetes. GLP-1 RA therapy is also consistent with patient values and preferences. Patients from our focus group ### Page 77 valued effective therapy and highlighted their struggles with prior attempts at weight loss using less effective treatments. While we feel many patients want to avoid pharmacological therapy, there is generally a more positive perception of GLP-1RA therapy due to commercials, social media, and interactions with friends and family who have experienced weight loss with the medication. They also value the multiple benefits of GLP-1RAs and the potential to reduce the use of other, less effective medications. While we find some patients hesitant to use injections, oral GLP-1 RA medications are currently being evaluated in clinical trials and, if available, may mitigate this concern. We acknowledge that many patients are concerned about being on GLP- 1RA long term; however, in patients with diabetes, this is less of a concern, as they are more accustomed to long-term therapy for their chronic condition. Overall, we feel patient values and preferences are similar across those with diabetes and prediabetes. We also considered resource use, acceptability, and feasibility as part of our recommendation. Resource use negatively impacted our recommendation. GLP-1 RA medications are currently very expensive for individuals and for health systems. We hope that generic medications and increasing market competition may mitigate this cost in the future. Similarly, supply availability has been highly variable, thus limiting the number of patients with access to therapy. We considered GLP-1 RA medication to be highly acceptable to providers because of its evidence of weight loss in T2DM and prediabetes, as well as providers being aware of multiple benefits, such as A1c reduction and potential cardiovascular benefits. We also considered these therapies to be feasible for the majority of patients. GLP-1 RA injectable pens are easy to use and can be administered in all outpatient settings with minimal teaching for most patients. Feasibility will only increase over time as more oral medications become available. The Work Group systematically reviewed evidence related to this recommendation.(279,321-324) Therefore, it is categorized as Reviewed, New-Added. The Work Group’s confidence in thequality of the evidence was low. The body of evidence had some limitations including lack of direct comparisons between patients with and without diabetes,(321,322) lack of primary weightloss outcome,(321) and a post hoc study design.(323) The benefits of GLP-1 RAs inobesity/overweight and co-occurring T2DM and prediabetes for weight loss, decreased abdominal circumference, and improved glycemic control outweighed the potential harm of adverse events. Patient values and preferences were similar because of the desire for more effective medications for weight loss and the multiple benefits of therapy. Thus, the Work Group decided upon a Weak for recommendation. Recommendation - 21. There is insufficient evidence to recommend either for or against orlistat, metformin, sodium glucose co-transporter type 2 inhibitors, or pramlintide for weight loss. (Neither for nor against | Reviewed, Amended) Discussion Evidence reviewed from SRs or RCTs published on or after April 1, 2019, to January 6, 2025, included Shi et al. (2024)(305). This systematic review network meta-analysis included 132trials enrolling 48,209 participants in total. The strength of the evidence was overall moderate. ### Page 78 Limitations include significant variability and heterogeneity in comparator interventions, given that lifestyle interventions were different even among studies looking at similar ages. Most studies included were funded by the pharmaceutical industry. Most were multicenter, and most included centers within the United States. Compared to lifestyle intervention at 24-52 weeks, across 52 randomized control trials, Shi et al. (2024) (305) found that orlistat did not lead to a clinically significant difference in percentbodyweight change (at least 5% weight loss). Similarly, in 13 RCTs,(305) metformin did not leadto a clinically important difference in percent bodyweight change at 24 to 52 weeks of follow-up. In 2 RCTs,(305) pramlintide also did not lead to a clinically important difference in percentbodyweight change at 24 to 52 weeks of follow-up when compared to lifestyle intervention. Finally, in 10 RCTs,(305) pramlintide also did not lead to a clinically important difference inpercent bodyweight change at 24 to 52 weeks of follow-up. The Work Group felt that there are benefits to having agents available that may assist with preventing weight gain associated with antipsychotic drug use, such as metformin, and agents that do not have significant central nervous system effects due to little systemic absorption, such as orlistat, and agents that treat comorbid conditions such as diabetes mellitus without causing weight gain, such as metformin, pramlintide and sodium glucose co-transport inhibitor therapies. These agents are largely oral (with the exception of pramlintide, which is a subcutaneous injection administered pre-meals), cost-effective, and promote equity since they can be prescribed by most providers. These benefits are however balanced with the potential harms of non-clinically significant weight loss seen with these agents, falling below the minimal important difference (MID) most often cited by the FDA of 5% body weight loss, as well as side effects associated with each, including gastrointestinal side effects of orlistat, metformin and pramlintide, as well as risk of genitourinary tract infections and euglycemic diabetic ketoacidosis risk from sodium glucose cotransport inhibitors if used in patients without sufficient endogenous insulin production remaining. (Note: when considering SGLT2i therapy, and it is unclear what endogenous insulin production remains, consider checking a postprandial glucose and C- peptide level to assess.) The Work Group systematically reviewed evidence related to this recommendation.(305)Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in the qualityof the evidence was moderate. The body of evidence had some limitations in that some agents had few studies evaluating their effects.(305) The benefits of orlistat, metformin, sodium glucoseco-transporter type 2 inhibitors, or pramlintide for weight loss were balanced with the potential harm, given the lack of overall efficacy for weight loss of these agents, less than the minimal important difference of 5% body weight change, while still causing adverse events, most often gastrointestinal. Patient values and preferences varied significantly because some patients prefer oral agents and do not prefer invasive treatments. Thus, the Work Group decided upon aNeither for nor against recommendation. ### Page 79 Recommendation - 22. There is insufficient evidence to recommend either for or against phentermine monotherapy, benzphetamine, diethylpropion, or phendimetrazine, for weight maintenance. (Neither for nor against | Reviewed, Amended) Discussion There are several medications approved by the FDA for short-term (i.e., “few weeks”) weightreduction (e.g., phentermine, benzphetamine, diethylpropion, and phendimetrazine). However, these approvals were based on studies conducted before 1975. The systematic evidence review carried out as part of this guideline update did not identify any current SRs or individual studies, from April 1, 2019 to January 6, 2025, that evaluated any of these agents that met the inclusion criteria. The prior 2020 VA/DOD Obesity CPG update found one small RCT compared diethylpropion (n=28) as one of five different medications (two not available in the U.S. [fenproporex, mazindol], one removed from the market [sibutramine], one off-label [fluoxetine]) to placebo (n=29) for weight loss in premenopausal women with obesity.(313) After 52 weeks,treatment with diethylpropion resulted in a significant weight reduction (-10.0 kg) compared to a placebo (-3.1 kg). In addition, 71.4% of patients treated with diethylpropion versus 33.3% ofpatients in the placebo group experienced a ≥5% reduction in body weight. Adverse events with diethylpropion included constipation, anxiety, and irritability, which were reported more frequently with treatment versus placebo. These sympathomimetic drugs are classified by the U.S. Drug Enforcement Administration as Schedule III or IV controlled substances, as they have potential for abuse, and prescribing information suggests they should not be used in individuals with a history of cardiovascular disease (CVD). The LEAP trial (Project Number5UH3HL155801-04), actively underway, should provide data on safety measures with longer-term use of phentermine. However, at the time of this writing, given the lack of additional data on long-term treatment in a large patient population, as well as the unknown long-term benefits and harms of intermittent short-term weight loss with this class of agents, the Work Group determined there was insufficient evidence to make a recommendation regarding the use of these medications for long-term use. It is important to recognize that these agents are oral medications that have been prescribed for decades. They are available in a generic formulation, which positively affects resource use, and are available at the VA, in military treatment facilities, and covered under Tricare. In addition, lower dose phentermine 15mg combined with extended release topiramate (phentermine/topiramate extended release [ER]) is FDA approved for long-term use (SeeRecommendation 18). The Work Group systematically reviewed evidence related to this recommendation, and no new studies were found to meet the inclusion criteria. The 2020 VA/DOD CPG update review found a single study, Suplicy et al. (2014), which provided low-quality evidence due to the small sample size. Therefore, it is categorized as Reviewed, Amended. The Work Group’s confidence in thequality of the evidence was low. The body of evidence had significant limitations, including small sample size, single-blind, and moderate to high attrition in a single study since 1975. Results from ### Page 80 an ongoing longer-term phentermine monotherapy study (LEAP, Long-Term Effectiveness of the Anti-obesity medication Phentermine, NCT05176626) remain pending as of this writing. The benefits of phentermine monotherapy, benzphetamine, diethylpropion, or phendimetrazine for weight maintenance were balanced with the potential harm. Patient values and preferences varied largely because some patients prefer a pharmacologic agent over no agent if no other agent is accessible financially. Thus, the Work Group decided upon a Neither for nor againstrecommendation. Recommendation - 23. We suggest against using dietary supplements or nutraceuticals for clinically meaningful weight management. (Weak against | Not reviewed, Amended) Discussion There is insufficient evidence demonstrating clinically significant short-term weight loss or supporting long-term weight management or maintenance through nutraceutical or dietarysupplements. A nutraceutical can be defined as “a food or dietary supplement that is believed toprovide health benefits”.(328) A combination of eight SRs and RCTs, which studied variousnutraceuticals, was identified and reviewed for this recommendation.(329-336) Overall, theconfidence in the quality of evidence was rated low to very low due to a lack of adequate randomization, blinding, allocation concealment, and high risk of bias. Inconsistent dosing of specific nutraceuticals and lack of generalizability of findings were noted across multiple studies. An SR of 15 RCTs (n=1,130) by Huang et al. (2018) showed a small but statistically significant weight loss of 0.89 kg (p=0.0006) with chitosan versus placebo for short-term weight loss (<24 weeks).(329) No serious adverse events were reported. The most commonly reported adverseevents were GI complaints (e.g., abdominal pain, bloating, constipation, indigestion, non- infectious diarrhea). The studies included in this large SR utilized multiple dosing regimens and used varying products and formulations of nutraceuticals, making dosing recommendations impossible. Mousavi et al. (2018) conducted an SR of 12 trials on the effects of cinnamon supplementation on obesity, finding statistically significant differences in short-term weight loss (-1.02 kg; p=0.002) and BMI (-0.39 kg/m2; p<0.001).(330) The generalizability of outcomes to the VA/DOD populationis limited. Specifically, of the 14 studies included in the systematic review, only three were conducted in Western cultures – two in the United States and one in the United Kingdom (U.K.); the remainder were conducted in the Middle East. Furthermore, at least half of the included studies included only female subjects. Additionally, inconsistent heterogeneous dosing of cinnamon was also noted. In reference to Garcinia Cambogia, a small randomized controlled trial conducted by Tripathy et al. (2013) demonstrated statistically significant (p<0.0001) short-term weight loss, as measured by Body Mass Index (BMI), following the consumption of Garcinia Cambogia for four months.(331)Limitations included a small study population (n=100) and non-stratified results between men and women. An online search of FDA warnings lists garcinia cambogia as a nutraceutical dietary ### Page 81 supplement that is sold as a combination supplement. When taken in that form, it is associated with risk for coronary disease events, stroke, and liver damage. Harms and burdens of Garcinia Cambogia outweigh the benefits. In addition, the FDA previously recalled a product being used for weight loss for being associated with reports of liver damage related to the ingredient hydroxycitric acid, an ingredient in Garcinia Cambogia products or dietary supplements. Considering the potential risks, harms, and burdens associated with Garcinia Cambogia, its limited benefits were deemed insufficient to justify its use. No statistically significant weight loss was observed when green tea was used in comparison to a placebo across the two studies reviewed.(332,333) Limitations included that comparators werenot the same between subject groups. Green tea was used in conjunction with other supplements, making it unclear whether green tea had a specific effect. Statistically significant weight loss was seen in one small RCT (n=60) looking at Phaseolus vulgaris over 12 weeks, with an MD in weight loss of 1.7 kg between Phaseolus vulgaris and control.(334) Phaseolus vulgaris is also known as the common bean, green bean, and Frenchbean. Adverse events were not severe, not serious, and not related to the supplement. Pill burden was a concern, with subjects taking six tablets per day. An SR of 15 studies using probiotics showed no statistically significant difference in weight loss outcomes versus placebo.(335) Limitations included the heterogeneity of supplements studied. A small RCT using raspberry ketones did not show a statistically significant outcome for weight loss for up to 12 weeks.(336) The study participants were all female. Furthermore, dietary supplements and nutraceuticals have not been extensively studied in conjunction with CLIs, resulting in insufficient evidence to determine whether the active dietary supplement or nutraceutical product is superior to a placebo when combined with CLI. Although there may be isolated supplements that are safe, these are rarely sold as individual ingredients and may be combined with other supplements that are not safe. Specifically, liver toxicity has been documented as a side effect of some weight loss supplements.(337,338) The Work Groupconsidered this aspect to be a fundamental component of any long-term weight management intervention. Additionally, marketing may be misleading when companies claim to treat or cure a disease without evidence to prove effectiveness.(339) The perceived advantages of dietarysupplements and nutraceuticals, often promoted through marketing and anecdotal reports, may create unrealistic expectations that hinder patient and clinician interest and investment in the evidence-based interventions recommended in this CPG. In the review of dietary supplements for weight loss, additional consideration was given to potential issues such as increased cost, safety, effectiveness, pill burden, and diverting patient interest away from evidence-based interventions. Concerns exist that supplements are frequently marketed to present inaccurate or exaggerated benefits at an excessive cost.(339) The FDAregulatory guidelines treat items listed as dietary supplements as a food, as defined by the Dietary Supplement Health and Education Act (DSHEA) of 1994.(340) Dietary supplements andnutraceuticals do not require investigation as a new drug.(340) The overall safety concerns, cost, ### Page 82 and pill burden using dietary supplements often complicate medical treatment and have the potential to delay treatment with effective therapeutics. The Work Group did not systematically review evidence related to this recommendation. The studies were obtained from the 2020 CPG. (329-336) Therefore, it is categorized as Not reviewed,Amended. The Work Group’s confidence in the quality of the evidence was low. The body ofevidence had many limitations including small sample sizes,(331) heterogeneity of supplementdosing and concentration,(330) use of a highly selective study population,(334) and risk forbias.(334). The supplements also have a risk of potential harm due to a lack of regulations andmonitoring, and drug interactions with prescribed medications; thus, the harms/burden slightly outweigh the benefits. Patient values and preferences varied significantly because of high costs, false advertising, and pill burden. Thus, the Work Group decided upon a Weak againstrecommendation. ### Page 83 # X. Research Priorities Obesity is a chronic, relapsing neurohormonal disease that is associated with over 200 other diseases. There are several areas that require more focused research to provide stronger evidence for further recommendation development across the spectrum of career recommendations and aid in refining interventions. In summary, the Work Group recommends research on comprehensive lifestyle interventions, dietary approaches, metabolic and bariatric surgery, pharmacotherapy, weight bias and stigma, and cost-effective strategies. Research on how to best implement CPG recommendations would be helpful in both the VA and DOD. ## A. Comprehensive Lifestyle Interventions Comprehensive lifestyle intervention (CLI) programs can be resource-intensive, particularly regarding training and retaining clinical staff and maintaining evidence-based program support tools (educational materials, technology-assisted programming). Therefore, more research is needed to identify accessible, scalable, and practical ways to deliver the three core elements ofthese programs (behavior change, nutrition, and physical activity) in ways that align with patients’abilities, values, and preferences. For example, comparative effectiveness studies to compare modes of CLI delivery as well as different intensities of CLI would inform refinements to recommendations and potentially more efficient resource utilization. In addition, trials evaluating how to optimally combine CLI with other interventions, particularly in light of newer, more effective pharmacotherapy, are needed. Research is also needed on the use of artificial intelligence (AI) tools to support CLI, particularly the use of data to provide individualized feedback and treatment tailoring, as well as trials evaluating AI-assisted delivery of behavioral weight management interventions. Additionally, research should examine how different types of exercise, especially when combined with obesity medications, impact body composition and health outcomes, while also evaluating adherence and attrition rates related to these interventions. ## B. Dietary Approaches Further research is needed to identify dietary approaches that are particularly effective in addressing appetite regulation and increasing satiety, which could play a key role in supporting long-term weight management. Well-designed studies should also focus on evaluating the effectiveness of various diets in promoting sustained weight loss over time. In addition, expanding research on the comparative health benefits of different dietary patterns could provide valuable insights for developing more personalized and outcome-driven dietary recommendations. Future research should prioritize investigating the nuanced role of micronutrient and macronutrient deficiencies, particularly protein and vitamins, in patients on obesity medications, to better understand their impact on treatment efficacy, safety, and long-term nutritional status. ## C. Metabolic and Bariatric Procedures and Surgery There is a growing need for research to evaluate the outcomes of metabolic and bariatric surgery (MBS) in individuals with Class 1 and 2 obesity who do not present with obesity-related comorbid conditions. Additionally, investigations should examine the interaction between MBS and emerging pharmacotherapies for obesity, as these medications may influence surgical outcomes or serve as alternatives in certain populations. Evidence for combination medications and ### Page 84 procedures is lacking. Comparative studies are also essential to determine the effectiveness and safety of surgery compared to pharmacotherapy. There is emerging evidence to support some obesity medications in the prevention of weight regain after metabolic and bariatric procedures and surgery.(341-343) Additional literature to assess the potential role of pharmacologic agents asadjuvant or neoadjuvant treatments in the context of bariatric surgery is essential to better understand optimal timing/sequencing of these interventions. The left gastric artery embolization (LGAE) procedure for obesity does not have full FDA approval for general use, but has been studied under experimental device exemptions and for pilot clinical trials by the FDA, such as the GET LEAN and BEAT Obesity studies. LGAE aims to reduce the hunger hormone ghrelin by decreasing blood flow to the stomach's fundus, potentially leading to weight loss. It is an experimental, minimally invasive procedure with promising early results but also potential complications, and requires further research to establish its safety and efficacy for treating obesity. ## D. Pharmacotherapy The individualization of pharmacotherapy plans is essential to ensure that patients receive the most effective and appropriate treatments tailored to their unique needs. This personalized approach is particularly crucial when considering insurance coverage and tapering obesity medications. As pharmacologic options for obesity expand, future research must prioritize a more individualized, equitable, biologically informed, and practical approach to treatment. Although long-term safety data for most established obesity medications exist, critical evidence gaps remain that limit optimal care delivery. Pharmacotherapy requires a highly individualized approach, informed by factors such as comorbidities, risk of sarcopenia in older adults, and psychiatric history. Yet most existing studies compare full-dose continuation to abrupt discontinuation, with limited data on stepwise dose reduction strategies that could optimize both tolerability and adherence. Comparative effectiveness studies in real-world populations are needed to guide decision-making between drug classes and in relation to other interventions. Additionally, cost-effectiveness analyses are crucial to inform policy, promote equitable access, and shape clinical guidelines. Underrepresented populations, including racial and ethnic minorities, individuals with specific genetic profiles, and those with coexisting medical and psychiatric conditions, remain largely excluded from clinical trials. Research must also explore the optimal duration of use, management of plateaus, management of treatment discontinuation, as well as long-term metabolic, cardiovascular, and psychological effects of treatment discontinuation to inform strategies for weight maintenance. Ongoing evaluation of long-term safety, especially in vulnerable populations such as peripartum and lactating women, is critical to ensure that expanding access to pharmacologic obesity care does not compromise long-term health. Future studies should investigate how genetic, metabolic, and behavioral phenotyping can enable precision medicine approaches, tailoring treatment to individual biology. Additionally, future research would explore when the optimal time is to start pharmacotherapy for individuals with overweight and obesity. To improve efficacy and durability, research must further elucidate the neurohormonal biology of obesity. Exploring biological targets beyond the GLP-1 axis may lead to ### Page 85 drugs with greater potency and fewer side effects, while combination therapies that address multiple mechanisms of appetite and energy regulation offer another promising direction. ## E. Weight Bias and Stigma Future research on weight bias and stigma should include fully powered randomized clinical trials that are inclusive and representative of active-duty Service members and Veterans. Studies should explore whether reducing weight stigma leads to improved engagement in weight loss treatments. Interventions targeting weight bias and discrimination among providers, particularly within the VA and DOD systems, are essential, with outcomes assessed for both providers and patients. Addressing obesity could lead to improved health outcomes and reduced healthcare expenditures. ## F. Cost-Effective Strategies Research should also examine the potential cost savings of treating obesity and preventing other consequential conditions such as hypertension, diabetes, obstructive sleep apnea, cardiovascular disease, and certain cancers. Obesity is a significant risk factor for these chronic diseases, which impose substantial economic burdens on healthcare systems. Effectively treating obesity could lead to improved health outcomes and reduced healthcare expenditures. ### Page 86 # Appendix A: Guideline Development Methodology ## A. Developing Key Questions to Guide the Systematic Evidence Review To guide this CPG’s systematic evidence review, the Work Group drafted 12 KQs on clinical topics of the highest priority for the VA and DOD populations. The KQs followed the population, intervention, comparison, outcome, timing, and setting (PICOTS) framework, as established by the Agency for Healthcare Research and Quality (AHRQ) (seeTable A‐1). Table A-1. PICOTS (344) Abbreviation: PICOTS: population, intervention, comparison, outcome, timing, and setting The Champions, Work Group, and evidence review team carried out several iterations of this process, each time narrowing the scope of the CPG and the literature review by prioritizing the topics of interest. Due to resource constraints, all developed KQs were not able to be included in the systematic evidence review. Thus, the Champions and Work Group determined which questions were of highest priority, and those were included in the review.Table A-4 contains thefinal set of KQs used to guide the systematic evidence review for this CPG. ### a. Population(s) - • The clinical population considered in this systematic review are adults (aged 18 years or older) with overweight or obesity. - • For KQ 12, the population of interest is the standard clinical population with one of the following co-occurring conditions: - • Type 2 diabetes, - • atherosclerotic cardiovascular disease (ASCVD) (including Congestive Heart Failure), or - • metabolic dysfunction-associated steatotic liver disease (MASLD) (aka non-alcoholic fatty-liver disease (NAFLD), MASH, etc.). ### Page 87 ### b. Interventions and Comparators ### Page 88 ### Page 89 ### c. Standard Pharmacotherapy List ### Page 90 ### d. Outcomes ### Page 91 ### Page 92 ### Page 93 ### e. Timing Standard timing: “weight loss” is weight at a minimum of 6 months of a program or intervention, and “weight maintenance” is 24 months and beyond. ### Page 94 ### f. Setting(s) Outpatient delivery of care (with the exception that some types of bariatric surgery may require inpatient care). ## B. Conducting the Systematic Review Extensive literature searches identified 11,129 citations potentially addressing the KQs of interest to this evidence review. Of those, 7,260 were excluded upon title review for clearly not meeting inclusion criteria (e.g., not pertinent to the topic, not published in English, published prior to study inclusion publication date, or not a full-length article). Overall, 3,869 abstracts were reviewed, with 3,218 of those being excluded for the following reasons: wrong study design, clearly did not address a KQ, did not report a population, intervention, comparator, or outcome of interest, had an inadequate sample size, were outside cutoff publication dates, or were included in an included SR. A total of 651 full-length articles thought to address one or more KQs were reviewed. Of those, 596 were excluded for the following reasons: wrong study design, clearly did not address a KQ, did not report a population, intervention, comparator, or outcome of interest, had an inadequate sample size, were outside cutoff publication dates, outside HDI region of interest, or were superseded by a more comprehensive SR or included in an included SR, these are presented inFigure A-1 below. Overall, 57 publications addressed one or more of the Key Questions and were considered as evidence in this review.Table A-2 indicates the number of studies that addressed each of theKQs. ### Page 95 Figure A-1. Study Flow Diagram ![Figure A-1. Study Flow Diagram]() ![Figure A-1. Study Flow Diagram]() ![Figure A-1. Study Flow Diagram]() ![Figure A-1. Study Flow Diagram]() ![Figure A-1. Study Flow Diagram]() ![A diagram of a flowchart]() Abbreviations: CS: comparative study; HDI: Human Development Index; KQ: key question; SR: systematic review ### Page 96 Alternative Text Description of Study Flow Diagram Figure A-1. Study Flow Diagram is a flow chart with nine labeled boxes linked by arrows thatdescribe the literature review inclusion-exclusion process. Arrows point down to boxes that describe the next literature review step, and arrows point right to boxes that describe the excluded citations at each step (including the reasons for exclusion and the numbers of excluded citations). ### Page 97 Table A-2. Evidence Base for KQs *Some papers address more than one KQ, and some studies are reported in more than one paper, therefore the total number for the evidence base is greater than the total number of includes in the study flow diagram and description. Abbreviations: KQ: key question; RCT: randomized controlled trial; SR: systematic review ### Page 98 ### a. General Criteria for Inclusion in Systematic Evidence Review - • Randomized control trials (RCTs) or systematic reviews of RCTs published on or after April 1, 2019, through January 6, 2025. If multiple systematic reviews addressed a key question, we selected the most recent and/or comprehensive review. - • Studies had to be published in English. - • Publication had to be a full clinical study or systematic review; abstracts alone were not included. Similarly, letters, editorials, research protocols, and other publications that were not full-length clinical studies were not accepted as evidence. - • Systematic reviews must have searched MEDLINE or EMBASE for eligible publications, performed a risk of bias assessment of included studies, and assessed the quality of evidence using a recognizable rating system, such as Grading of Recommendations Assessment, Development and Evaluation (GRADE) or something compatible (e.g., the tool used by the AHRQ Evidence-based Practice Centers [AHRQ-EPCs]). If an existing review did not assess the overall quality of the evidence, evidence from the review must have been reported in a manner that allowed us to judge the overall risk of bias, consistency, directness, and precision of evidence. We did not use an existing review as evidence if we were not able to assess the overall quality of the evidence in the review. - • Randomized control trials must have had an independent control group. Randomized crossover trials were only included if data from the first period (prior to treatment crossover) was reported separately and an adequate washout period was used. - • Study must have enrolled at least 20 patients (10 per study group for RCTs and 20 for prospective non-randomized studies) unless otherwise noted (seeKey QuestionSpecific Criteria below). - • Study must have enrolled at least 85% of patients who met this SR’s populationcriteria: adults aged 18 years or older with overweight or obesity. If the patient population fell below this threshold but the relevant population were reported separately, then that study was included. - • To ensure applicability to the VA/DOD healthcare systems, and ensure consistency across the CPG program, inclusion of individual studies was limited to very highHuman Development Index (HDI), countries with an index ≥0.8 where standards ofhealthcare are comparable (e.g., United States, Canada, United Kingdom, Western Europe, Israel, Japan, Hong Kong, Australia, and New Zealand). Inclusion of systematic reviews was limited to those including more than half of the studies from eligible regions. - • These regions of interest are listed in Table 1 of the Statistical Annex of the[2023/24Human Development Report](https://hdr.undp.org/system/files/documents/global-report-document/hdr2023-24reporten.pdf) produced by the United Nations DevelopmentProgramme. - • Study must have reported on at least one outcome of interest. ### Page 99 ### b. Key Question Specific Criteria for Inclusion in Systematic Evidence Review - • If no RCTs are available to address KQ 6, prospective, non-randomized comparative studies were included. In the event there is no data identified for this KQ, we then looked at longitudinal cohort studies. Similarly, if no systematic reviews of RCTs are available for KQ 6, SRs of eligible non-RCT designs were used. - • For KQ 12, RCTs and SRs of RCTs that performed subgroup analyses of the specified co-occurring conditions were included. We also considered SRs of observational studies that compare treatment effects in patients with and without the specified co-occurring conditions. ### c. Literature Search Strategy Information regarding the bibliographic databases, date limits, and platform/provider can be found inTable A-3, below. Additional information on the search strategies, including topic-specificsearch terms and search strategies can be found inAppendix F. Table A-3. Bibliographic Database Information ### d. Rating the Quality of Individual Studies and the Body of Evidence The Sigma Team assessed the methodological risk of bias of individual diagnostic, observational, and interventional studies using the USPSTF method. Each study is assigned a rating of Good,Fair, or Poor based on a set of criteria that vary depending on study design. Detailed lists of criteria and definitions appear in Appendix VI of the USPSTF procedure manual.(345) Next, the Sigma team assessed the overall quality of the body of evidence for each critical and important outcome using the GRADE approach. This approach considers the following factors: overall study quality (or overall risk of bias or study limitations), consistency of evidence, directness of evidence, and precision of evidence. The overall quality of the body of evidence is rated as High, Moderate, Low, and Very Low. ### Page 100 ## C. Developing Evidence-Based Recommendations In consultation with the VA Office of Quality and Patient Safety and the Clinical Quality Improvement Program, Defense Health Agency, and the Sigma Team convened a 3.5-day in- person recommendation development meeting from April 8-11, 2025, to develop this CPG’sevidence-based recommendations. Two weeks before the meeting, the Sigma Team finalized the systematic evidence review and distributed the report to the Work Group; findings were also presented during the recommendation development meeting (seeDetermining RecommendationStrength and Direction). Led by the Champions, the Work Group interpreted the systematic evidence review’s findings and developed this CPG’s recommendations. The strength and direction of each recommendationwere determined by assessing the quality of the overall evidence base, the associated benefits and harms, patient values and preferences, and other implications. ### Determining Recommendation Strength and Direction Per GRADE methodology, to assess the quality of the evidence base and assign a grade for the strength of each recommendation. The GRADE system uses the following four domains to assess the strength of each recommendation:(81) #### 1. Confidence in the Quality of the Evidence Confidence in the quality of the evidence reflects the quality of the evidence base and the certainty in that evidence. This second domain reflects the methodological quality of the studies for each outcome variable. In general, the strength of recommendation follows the level of evidence, but not always, as other domains may increase or decrease their strength. The evidence review used for the development of recommendations for overweight and obesity, conducted by the Sigma Team, assessed the confidence in the quality of the evidence base andassigned a rate of “High,” “Moderate,” “Low,” or “Very Low.” The elements that go into the confidence in the quality of the evidence include: - • Is there high or moderate quality evidence that answers this question? - • What is the overall certainty of this evidence? #### 2. Balance of Desirable and Undesirable Outcomes Balance of desirable and undesirable outcomes refers to the size of anticipated benefits (e.g., increased longevity, reduction in morbid events, resolution of symptoms, improved quality of life, decreased resource use) and harms (e.g., decreased longevity, immediate serious complications, adverse events, impaired quality of life, increased resource use, inconvenience/hassle) relative to each other. This domain is based on the understanding that most providers will offer patients therapeutic or preventive measures if the advantages of the intervention exceed the risks and adverse effects. The certainty or uncertainty of the provider about the risk-benefit balance will greatly influence the strength of the recommendation. Some of the discussion questions that fall under this domain include: ### Page 101 - • Given the best estimate of typical values and preferences, are you confident that the benefits outweigh the harms and burden or vice versa? - • Are the desirable anticipated effects large? - • Are the undesirable anticipated effects small? - • Are the desirable effects large relative to undesirable effects? #### 3. Patient Values and Preferences Patient values and preferences is an overarching term that includes patients’ perspectives,beliefs, expectations, and goals for health and life. More precisely, it refers to the processes that individuals use in considering the potential benefits, harms, costs, limitations, and inconvenienceof the therapeutic or preventive measures in relation to one another. For some, the term “values” has the closest connotation to these processes. For others, the connotation of “preferences” bestcaptures the notion of choice. In general, values and preferences increase the strength of the recommendation when there is high concordance and decrease it when there is great variability. In a situation in which the balance of benefits and risks are uncertain, eliciting the values and preferences of patients and empowering them and their surrogates to make decisions consistent with their goals of care becomes even more important. A recommendation can be described ashaving “similar values,” “some variation,” or “large variation” in typical values and preferencesbetween patients and the larger populations of interest. Some of the discussion questions that fall under the purview of values and preferences include: - • Are you confident about the typical values and preferences and are they similar across the target population? - • What are the patient’s values and preferences? - • Are the assumed or identified relative values similar across the target population? #### 4. Other Implications Other implications consider the practicality of the recommendation, including resources use, equity, acceptability, feasibility and subgroup considerations. Resource use is related to the uncertainty around the cost-effectiveness of a therapeutic or preventive measure. For example, statin use in the frail elderly and others with multiple co-occurring conditions may not be effective and depending on the societal benchmark for willingness to pay, may not be a good use of resources. Equity, acceptability, feasibility, and subgroup considerations require similar judgments around the practicality of the recommendation. The framework below (Table A-4) was used by the Work Group to guide discussions on eachdomain. ### Page 102 Table A-4. GRADE Evidence to Recommendation Framework ## D. Recommendation Categorization ### 5. Recommendation Categories and Definitions For use in the 2025 OBE CPG, a set of recommendation categories was adapted from those used by the United Kingdom National Institute for Health and Clinical Excellence (NICE).(86,87) Thesecategories, along with their corresponding definitions, were used to account for the various ways in which recommendations could have been updated from the 2020 OBE CPG. The categories and definitions can be found inTable 3. ### Page 103 #### 6. Categorizing Recommendations with an Updated Review of the Evidence Recommendations were first categorized by whether they were based on an updated review ofthe evidence. If evidence had been reviewed, recommendations were categorized as “New-added,” “New-replaced,” “Not changed,” “Amended,” or “Deleted.” “Reviewed, New-added” recommendations were original, new recommendations that were not inthe 2020 OBE CPG. “Reviewed, New-replaced” recommendations were in the previous version ofthe guideline but were modified to align with the updated review of the evidence. These recommendations could have also included clinically significant changes to the previous version.Recommendations categorized as “Reviewed, Not changed” were carried forward from theprevious version of the CPG unchanged. Recommendations could have also been designated “Reviewed, Deleted.” These wererecommendations from the previous version of the CPG that were not brought forward to the updated guideline after review of the evidence. This occurred if the evidence supporting the recommendations was out of date, to the extent that there was no longer any basis to recommend a particular course of care and/or new evidence suggests a shift in care, rendering recommendations in the previous version of the guideline obsolete. #### 7. Categorizing Recommendations without an Updated Review of the Evidence There were also cases in which it was necessary to carry forward recommendations from the previous version of the CPG without an SR of the evidence. Due to time and budget constraints, the update of the OBE CPG could not review all available evidence on management of overweight and obesity, but instead focused its KQs on areas of new or updated scientific research or areas that were not previously covered in the CPG. For areas of research that have not changed, and for which recommendations made in the previous version of the guideline were still relevant, recommendations could have been carried forward to the updated guideline without an updated SR of the evidence. The support for these recommendations in the updated CPG was thus also carried forward from the previous version ofthe CPG. These recommendations were categorized as “Not reviewed.” If evidence had not beenreviewed, recommendations could have been categorized as “Not changed,” Amended,” or “Deleted.” “Not reviewed, Not changed” recommendations refer to recommendations from the previousversion of the OBE CPG that were carried forward unchanged to the updated version. Thecategory of “Not reviewed, Amended” was used to designate recommendations that were modified from the 2020 CPG with the updated GRADE language, as explained above. Recommendations could also have been categorized as “Not reviewed, Deleted” if they weredetermined to be out of scope. A recommendation was out of scope if it pertained to a topic (e.g., population, care setting, treatment, condition) outside of the scope for the updated CPG as defined by the Work Group. ### Page 104 The categories for the recommendations included in the 2020 version of the guideline are noted in theRecommendations. Recommendations 2, 3, 4, 22, and 23 were carried forward from the 2020OBE CPG using this method. The categories for the recommendations from the 2020 OBE CPG are noted inAppendix C. ## E. Drafting and Finalizing the Guideline Following the face-to-face meeting, the Champions and Work Group members were given writing assignments to craft discussion sections to support each of the new recommendations and/or to update discussion sections from the 2020 OBE CPG to support the amended “carried forward”recommendations. The Work Group also considered tables, appendices, and other sections from the 2020 OBE CPG for inclusion in the update. During this time, the Champions and Work Group also made additional revisions to the algorithms, as necessary. After developing the initial draft of the updated CPG, an iterative review process was used to solicit feedback on and revise the CPG. Once they were developed, the first two drafts of the CPG were posted on the OBE Wiki Website for a period of 10-20 business days for internal review and comment by the Work Group. Draft 3 was made available for a 14-day peer review and comment period (seeExternal Peer Review). All feedback submitted during each review period wasreviewed and discussed by the Work Group, and appropriate revisions were made to the CPG. Following the Draft 3 review and comment period, the Work Group reviewed external feedback and created a final draft of the CPG. The Champions then presented the CPG to the VA/DOD EBPWG for approval, and the final CPG was approved in October 2025. To accompany the CPG, the Work Group produced toolkit products, including a provider summary, quick reference guide, and patient summary. ### Page 105 # Appendix B: Evidence Table Table B-1. 2025 Overweight/Obesity Evidence Table 1, 2, 3, 4 ### Page 106 ### Page 107 ### Page 108 ### Page 109 ### Page 110 # Appendix C: 2020 Recommendation Categorization Table C-1. 2020 Overweight and Obesity CPG Recommendation Categorization Table 1, 2, 3 ### Page 111 ### Page 112 ### Page 113 # Appendix D: Participant List Natasha Antonovich, PharmD, BCPS National PBM Clinical Pharmacy Program Manager Neurology, Weight Management, Solid Organ Transplant, Drug Interactions Orlando, FL Erin J. Arra, MS, RDN, CSOWM, LD MOVE! Weight Management Program Coordinator VISN 10 MOVE! Weight Management Coordinator VA Northeast Ohio Healthcare System Wade Park Division Cleveland, OH Tara Bastawrous, PharmD, BCPS, BC- ADM Patient Centered Medical Home Clinical Pharmacist Walter Reed National Military Medical Center Bethesda, MD Elizabeth M. Bauer, MD, FACP, FACE, Dipl. ABOM Endocrinology Staff and Endocrinology- Rheumatology Service Chief Naval Medical Center San Diego Clinical Associate Professor, InternalMedicine, USUHS San Diego, CA Richele Corrado, DO, MPH, FACP, Dipl.ABOM Internist & Obesity Medicine Specialist Clinical Associate Professor of Medicine, Department of Medicine, Uniformed Services University of the Health Sciences Revolution Medicine, Health & Fitness, Washington, DC Dan Eisenberg, MD, MS, FACS Professor of Surgery, Stanford School of Medicine Director of Bariatric and Minimally Invasive Surgery, VA Palo Alto Health Care System Bariatric Surgeon Palo Alto, CA Denise Gratias, MSN, NP, ACNP-BC Endocrine/Obesity Nurse Practitioner Long Beach, CA Andrew T. Harris, MD Director of Systems Improvement, Primary Care Northeast Ohio VA Healthcare System Cleveland, OH Marija S. Kelber, PhD Team Lead, Evidence Synthesis and Dissemination Psychological Health Center of Excellence (PHCoE) Research and Engineering (R&E) Defense Health Agency (DHA) Silver Spring, MD Jenna Klimovich, MD Internist, Primary Care West Haven, CT Megan Kloetzel, MD, MPH, CIC, Dipl. ABOM Defense Health Network Indo-Pacific (DHN- IP) DAD-CQM Honolulu, HI Jared S. Magee, DO, MPH, FACP, Dipl. ABOM, MAJ, MC, USA Gastroenterologist, Walter Reed National Military Medical Center Gastroenterology Product Line Chair, National Capital Region Associate Program Director, Gastroenterology Fellowship, National Capital Consortium Assistant Professor of Medicine, Uniformed Services University of the Health Sciences Bethesda, MD ### Page 114 Robin Masheb, PhD Director, Veterans Initiative for Eating and Weight, (The VIEW), VA CT Healthcare System Director of Education, PRIME Center, VA CT Healthcare System Professor of Psychiatry, Yale School of Medicine New Haven, CT Stéphanie B. Mayer, MD, MHSc, Dipl. ABCL, Dipl. ABOM Associate Professor Division of Endocrinology, Diabetes, and Metabolism Central Virginia Veterans Affairs Health Care System and Virginia Commonwealth University MOVE! Program Champion, Central Virginia VA Healthcare System Diplomate American Board of Clinical Lipidology Diplomate American Board of Obesity Medicine Richmond, VA Susan D. Raffa, PhD, FSBM National Program Director for Weight Management VHA National Center for Health Promotion and Disease Prevention (NCP, 12NCHP) Durham, NC Quinn Romasko, DPT, CPT, SP Staff Physical Therapist Warrior Ohana Medical Home Tripler Army Medical Center Tripler AMC, HI Jeanette K. Sanders, Lt, Col, UASF, NC 82d Chief Nurse Sheppard AFB, TX Natalia Weare-Regales, MD Associate Professor of the Endocrinology Department of the University of South Florida Program Director for the Endocrinology Department of the University of South Florida Tampa, FL ### Page 115 # Appendix E: Patient Focus Group Methods and Findings ## A. Methods VA and DOD Leadership recruited five participants for the focus group, with support from the Champions and other Work Group members as needed. A convenience sample was utilized in the selection of participants, and therefore, the sample of patients used is not generalized for the entirety of VA and DOD patients who have experience with overweight and obesity. The goal of recruitment for this Patient Focus Group was to have a group of engaging, diverse patients receiving VA or DOD healthcare services, who could cogently explain their experience with overweight and/or obesity. Participants were not incentivized for their participation or reimbursed for travel expenses. The Work Group, with support from the Sigma Team, identified topics on which patient input was important to consider in developing the CPG. The Sigma Team developed, and the Work Group approved, and patient focus group guide covering these topics. The focus group facilitator led the discussion and used the guide to elicit the patients’ perspectives about their treatment and overallcare. Given the limited time and the range of interests of the focus group participants, not all questions were addressed. ## B. Patient Focus Group Findings ### a. Participants value communication and shared decision making with providers in accessing obesity medications and treatment. - • Participants value advocacy for the patient when seeking a provider. - • Participants discussed the complexities in obtaining and maintaining weight management treatments. ### b. Participants highlighted the challenges of weight management due to age, medical conditions, and personal circumstances, emphasizing the importance of individualized treatment plans in weight loss and weight management. - • Participants shared the challenges they and their colleagues have faced related to their weight. - • Participants emphasized the importance of goal setting and individualized treatment plans in weight loss and weight maintenance. ### c. Participants discussed the impact that their weight treatment has had on their mental health and career aspirations, emphasizing the need for effective weight management to maintain career standards and personal well-being. - • Participants raised stigma as an issue while dealing with their weight. - • Participants shared their experience with depression and body dysmorphia. - • Participants shared strategies to maintain their personal well-being during weight loss and weight maintenance. ### Page 116 ### d. Participants emphasized the value of non-pharmacological therapies and lifestyle changes when managing weight. - • Participants engaged in various physical activities, including mind and body groups, yoga, swimming, aquatic therapy, and extra high-intensity, short-duration workouts. - • Participants utilized mindfulness-based stress reduction techniques. - • Participants substituted healthier food options for processed foods. ### e. In order to reduce the stigma of overweight and obesity, participants discussed the value of providers expressing empathy and patience when working with patients on weight loss and weight maintenance. - • Participants feel discouraged when providers tell them to lose weight as if it is a given, rather than offering supportive guidance. - • Participants felt belittled when providers used a negative tone/stigmatizing language about weight loss instead of engaging in goal-setting discussions. ### f. Participants emphasized the need for better communication and support from healthcare providers. - • Participants experienced delays in care and medication refills when their current provider was deployed, highlighting the need for continuity of care. - • Participants preferred to receive information from their weight management specialist, emphasizing the importance of specialized care. ### Page 117 # Appendix F: Literature Review Search Terms and Strategy The search strategies employed combinations of free-text keywords as well as controlled vocabulary terms including (but not limited to) the following concepts. Strategies for each bibliographic database follow this table. Table F-1. Embase/Medline Search Strategy (Embase.com syntax) ### Page 118 ### Page 119 ### Page 120 ### Page 121 ### Page 122 Table F-2. PsycInfo Search Strategy (EBSCO syntax) ### Page 123 ### Page 124 Table F-3. PubMed in process Search Strategy (PubMed syntax) ### Page 125 ### Page 126 ### Page 127 ### Page 128 ### Page 129 Table F-4. AHRQ Evidence-based Practice Center Reports Search Strategy Table F-5. VA Evidence Synthesis Program Reports Search Strategy ### Page 130 # Appendix G: Alternative Text Descriptions of Algorithm The following outline narratively describes the Management of Overweight and Obesity in Adults OBEAlgorithm. An explanation of the purpose of the algorithm and description of the variousshapes used within the algorithm can be found in theAlgorithm section. The sidebars referencedwithin this outline can also be found in theAlgorithm section. ## Algorithm Module - 1. The Algorithm Module begins with Box 1, in the shape of a rounded rectangle: “Adults enrolled in the VA/DOD Health System” - 2. Box 1 connects to Box 2, in the shape of a rectangle: “With permission, offer guidanceabout behavioral strategies that support healthy eating and physical activity to maintain health (see Sidebar 1)” - 3. Box 2 connects to Box 3, in the shape of a rectangle: - - a. “Measure height and weight - - b. Calculate BMI to screen for overweight or obesity at medical visits - - c. Consider measuring waist circumference and other measures of adiposity”. - 4. Box 3 connects Box 4, in the shape of a hexagon, asks the question: “BMI ≥ 25 kg/m2? - - a. If the answer is “Yes” to Box 4, then Box 5. - - b. If the answer is “No” to Box 3, then Box 2, in the shape of a rectangle: “Withpermission, offer guidance about behavioral strategies that support healthy eating and physical activity to maintain health (see Sidebar 1)” - 5. Box 5, in the shape of a hexagon, asks the question: “Is patient ready to engage in treatment modalities?” - - a. If the answer is “Yes”, then Box 6, in the shape of a rectangle: - i. “Evaluate for factors contributing to obesity (see Sidebars 2 and 3) - ii. Assess for overweight- and obesity-associated conditions including laboratory and diagnostic testing (e.g., lipid panel, HbA1c, CMP, FIB-4, etc.) (see Sidebar 4) - iii. Assess for medications that cause weight gain” - - b. If the answer is “No”, then Box 2, in the shape of a rectangle: “With permission,offer guidance about behavioral strategies that support healthy eating and physical activity to maintain health (see Sidebar 1)” - 6. Box 6 connects to Box 7, in the shape of a rectangle: “Offer a Comprehensive LifestyleIntervention (see Sidebar 5)” - 7. Box 7 connects to Box 8, in the shape of a rectangle: “Consider Pharmacotherapy (seeSidebar 6), Endoscopic/Bariatric Procedures (see Sidebar 7), and/or Metabolic/Bariatric Surgery (see Sidebar 8), for appropriate candidates” - 8. Box 8 connects to Box 9, in the shape of a hexagon, asks the question: “Has patient achieved weight management goals?” - - a. If the answer is “Yes”, then Box 10, in the shape of a rectangle: “Continue CLI andany additional therapy for weight management, health maintenance, and treatment follow-up” - - b. If the answer is “No”, then Box 6, in the shape of a rectangle: - i. “Evaluate for factors contributing to obesity (see Sidebars 2 and 3) ### Page 131 - ii. Assess for overweight- and obesity-associated conditions including laboratory and diagnostic testing (e.g., lipid panel, HbA1c, CMP, FIB-4, etc.) (see Sidebar 4) - iii. Assess for medications that cause weight gain” ### Page 132 # Appendix H: Dietary Approaches For all the diets listed below, formal consultation with a registered nutritional dietitian is advised. The Academy of Nutrition and Dietetics (Academy) Evidence Analysis Library (EAL) Adult Weight Management Guideline (2014)(353,354) found strong evidence that weight loss, weightmaintenance, and a nutritionally adequate diet with adjusted calories should be part of a comprehensive weight management program that also includes appropriate physical activity and behavioral strategies. This is supported by the 2024 Academy Position Statement for treating overweight and obesity.(355) The Academy EAL guideline further states that, “the registereddietitian (or international equivalents) should prescribe client-centered interventions based oneach client’s needs, circumstances, and goals.”. Calorie reduction can be achieved by one of the following: ## A. Caloric and Nutritional Recommendations - • When in the healthcare setting in which direct or indirect calorimetry is not available, and estimating resting energy expenditure (REE), the Mifflin St. Jeor equation and actual body weight have the most accuracy for estimating calorie needs for those with overweight or obesity.(356) - -  A 500 to 750 energy deficit/day that contributes to a negative energy balance. - -  A 30% energy deficit may be used for estimating caloric reduction to achieve negative energy balance.(357) - • A reduction to 1,200 to 1,500 kcal per day for women and 1,500 to 1,800 kcal per dayfor men, adjusted based on the individual’s body weight, may be used when there is limited information about an individual. - • Individuals should focus on consuming nutrient-dense foods that are satiating, like protein and fibrous foods, while limiting foods that are energy-dense and not satiating. - • Individuals should focus on consuming nutrient-dense, minimally processed foods over ultra-processed energy-dense foods. - • Individuals should select eating plans that are easy to adhere to while trying to consider the above recommendations. - • The Dietary Reference Intake (DRI) Calculator for Healthcare Professionals(358) is atool that can be utilized by healthcare professionals to estimate daily caloric needs, BMI, and recommended intakes of macronutrients, water, vitamins, and minerals based on DRI data. Many dietary approaches can be used to achieve a negative energy balance/calorie reduction. The systematic evidence review conducted for this CPG update did not yield any exhaustive review of the various dietary approaches that may be considered for weight loss and weight maintenance; therefore, the dietary approaches described in this appendix do not encompass the totality of evidence-based approaches that a patient and healthcare provider may consider. TheAcademy Position Statement recommends “interventions based on shared decision making and ### Page 133 clinical judgement” and adjusted for “clients' value specific, tailored and usable diet and exerciseplans.” Table H-1 provides a summary of dietary approaches for which evidence exists to support weightloss when accompanied by an energy deficit/negative energy balance. For all the diets listed below, formal consultation with a registered dietitian is advised for at least five interactive sessions when feasible.(354) Table H-1. Dietary Approaches to Support Weight Management ### Page 134 More Dietary Approaches can be found in Medical Nutrition Therapy Interventions provided by Dietitians for Adult Overweight and Obesity Management: An Academy of Nutrition and Dietetics Evidence-Based Practice Guideline. J Acad Nut Diet 2023:23(3):520-545.[doi: https://doi.org/10.1016/j.jand.2022.11.014](https://www.jandonline.org/article/S2212-2672(22)01200-X/fulltext)(354) a For further information about the Mediterranean eating pattern see the 2020-2025 Dietary Guidelines for Americans, available at: https://www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020- 2025.pdf b For further information on the DASH dietary pattern visit:[https://www.nhlbi.nih.gov/health-topics/dash-eating-plan](https://www.nhlbi.nih.gov/health-topics/dash-eating-plan) andhttps://www.dietaryguidelines.gov/sites/default/files/2021-03/Dietary_Guidelines_for_Americans-2020-2025.pdf Abbreviations: ACC: American College of Cardiology; ADF: alternate-day fasting; AHA: American Heart Association; DASH: Dietary Approaches to Stop Hypertension; g: grams; kg: kilograms; LDL: low-density lipoprotein; mg: milligrams; RDA: recommended dietary allowance; SR: systematic review; TOS: The Obesity Society; TRE: Time-restricted eating; USDA: United States Department of Agriculture ### Page 135 # Appendix I: Physical Activity Approaches For all the strategies listed below, the Work Group recommends emphasizing the benefits of any amount of physical activity over none. While many may have difficulties in following specific recommendations, patients should be encouraged that any increase in activity will have benefits for weight management and health outcomes. Physical activity plans should be structured, individualized, and align with patient-centered goals, medical status, and preferences. Regular physical activity is a key component of a comprehensive lifestyle intervention and has additional benefits for general health, cardiometabolic health, mental well-being, and functional capacity.(212,360) Patients may increase their activity from planned exercise or non-exercise physical activities. ## A. Non-Exercise Activity - • Accounts for the majority of variation in a patient’s total daily caloric expenditure. - • Includes conscious activity (walking upstairs instead of taking an elevator) or spontaneous/subconscious activity (fidgeting while sitting at a desk or posture). - • Step counts are a useful way to monitor this. Higher daily step counts are associated with weight loss, cardiovascular health (CV), decreased all-cause and CV mortality, and improved cardiometabolic risk factors. - -  2,600-4,000 steps/day→initial benefits - -  Progressive risk reduction up to approximately 8,000–10,000 steps/day.(201,212,360-363) - • Increasing daily step count is an evidence-based, accessible intervention for managing obesity and improving cardiovascular health, with benefits seen well below the traditional 10,000 steps/day target.(212,360,364,365) There is a dose-dependent response to the amount of physical activity and intensity: - • For moderate intensity, <150 minutes per week → minimal weight loss; prevention of weight gain - • 150-225 minutes per week → small weight loss; prevention of weight gain - • 225-420 minutes per week → moderate weight loss (<3 kg) - • For vigorous activity, approximately half of this time for each category is needed - • Modest caloric restriction added to aerobic physical activity amounts per above will enhance weight loss Patients who have lost weight may also benefit from balance training to improve potential deficits in kinesthetic awareness that may accompany weight loss.(212) ## B. Patient Preference - • Patient adherence must be of primary focus given the critical impact of exercise on health, prevention of weight gain, and modest impacts on weight loss. Thus,Table I-1below highlights common types of physical activities for patient experimentation. - • Common themes for higher adherence are: ### Page 136 -  Group classes for social aspects and accountability -  Sports/recreational activities for enjoyment or the motivation of competition -  Low-impact activities that are less pain-provoking or therapeutic -  Ease of implementation into daily schedule -  Choosing a competition/race/event involving a chosen mode of exercise -  Of note, patients should be encouraged to add any of these themes to their favorite modalities of exercise. For example, someone who enjoys walking/jogging may enjoy joining a running club or signing up for a race. -  Impacts on hunger -  Different modalities of exercise can have differing impacts on hunger for different patients. They may increase or decrease hunger in different types of patients. Hence, patients should be encouraged to experiment.(360) - - • Cycling (outdoor or indoor) - - • Hiking - - • Jogging/Running - - • Jumping rope - - • Kayaking/Canoeing - - • Rowing - - • Swimming - - • Brisk walking Table I-1. Common Types of Physical Activities with Higher Patient Adherence ### Page 137 # Appendix J: Pharmacotherapy ## A. Medications FDA-Approved for Weight Maintenance The following tables summarize pharmacotherapy options for the long-term treatment of weight loss and maintenance. Refer to eachdrug’s prescribing information for full details. Included inTable J-1 are dose escalation titrations for each medication per manufacturer labeling. However, titrations should beindividualized based on patient tolerance and response. Many patients do not need higher dosages of obesity medications to reach desired goals, and patients tolerate best if titrated slowly. A weight loss goal of about 0.5-2lbs per week with optimal nutrition, physical activity, sleep, stress management, and the appropriate individualized dose for the patient should be practiced. Rapid and large amounts of weight loss may be associated with increased loss of skeletal muscle, vitamin deficiencies, and gallstone formation. ### Page 138 ### Page 139 ### Page 140 ### Page 141 a If applicable, refer to VA ([https://www.va.gov/formularyadvisor/](https://www.va.gov/formularyadvisor/)) or DOD ([http://www.health.mil/PandT](http://www.health.mil/PandT)) guidance/criteria for further recommendations on use of theseagents Abbreviations: CIV: Schedule IV controlled substance; CNS: central nervous system; CrCl: creatinine clearance; ER: extended-release; FDA: U.S. Food and Drug Administration; GI: gastrointestinal; GLP-1: glucagon-like peptide-1; IV: intravenous; MACE: major adverse cardiovascular events (for semaglutide this includes cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke); MAOI: monoamine oxidase inhibitor; MEN2: multiple endocrine neoplasia type 2; NuSH: nutrient-stimulated hormonal therapies; OSA: obstructive sleep apnea; PI: prescribing information; REMS: Risk Evaluation and Mitigation Strategy; subQ: subcutaneously; URTI: upper respiratory tract infection; XR: extended-release ### Page 142 Abbreviations: OR: odds ratio ### Page 143 ## B. Medications and Potential Weight Gain In the overall management of patients with obesity or overweight, it is critical to consider the impact of prescribed medications on the potential for weight gain and whether alternate medications may be a more appropriate option for patients who have overweight, obesity, or atrisk. Providers should review the patient’s current medications for any medications that may becontributing to increased weight. The side effect of weight gain, and potentially additive effect when more than one obesogenic medication is prescribed, should be considered when prescribing a medication for a patient in whom weight gain may be of concern. If an alternate medication is not an option, participation in a weight management program and weight monitoring may benefit the patient whose only option is a medication associated with weight gain. The information in is provided as only one aspect of medication selection for a patient withoverweight or obesity (or at risk for transition to overweight or obesity). Optimal medication management should take into account the potential effect on weight, as well as other patient factors, efficacy, safety, and available long-term outcome data. ## C. Off-Label Pharmacotherapy Several drugs have been used off-label as a long-term treatment for weight loss.(366-368) Belowis a list and brief discussion of some of these medications. ### a. Topiramate (Monotherapy) Weight loss was noted as a side effect when topiramate was used to treat epilepsy. A mean of 3.9 kg is lost at three months and 5.9 kg at one year, although the amount of weight loss tends to be greater in those with a higher BMI. Studies that have identified greater weight loss with higher doses have reported a ceiling effect at a dose of 192 mg/day.(369) A meta-analysis that included 3,320 patients with obesity from 10 studies (19 treatment arms) comparing topiramate (64 mg – 400 mg/day as a weight loss agent) to placebo over periods of 16 to 60 weeks found that the mean weight loss experienced by patients taking topiramate was 5.34 kg greater than with placebo. The amount of weight loss was a function of both dosage and duration of exposure. Safety data were available for 6,620 patients. The risk of study withdrawal due to an adverse event was greater for topiramate-treated patients (OR: 1.95) and was associated with a higher dosage. This same dose-related pattern was observed with the other common adverse events, including paresthesia, taste change or dysgeusia, psychomotor impairment, hypoesthesia, difficulty concentrating, anorexia, memory impairment, and nervousness.(370) In a meta-analysis of patients with obesity and T2DM, topiramate reducedweight and HbA1c; however, serious and total number of adverse events occurred more frequently with treatment.(371) Topiramate has also been used for binge eating disorder. In a meta-analysis including three RCT studies of 528 patients with binge eating disorder, Nourredine et al. (2021) found that topiramate reduced the number of binge eating episodes per week (MD = -1.31; 95% CI = -2.58 to –0.03), the number of binge days per week (MD = -0.98; 95% CI –1.80 to –0.16), as well as weight (MD = -4.91 kg;95% CI = -6.42 to –3.41).(372) However, patients in the topiramate arms alsodiscontinued study drug more frequently due to safety concerns (RR = 1.90; 95% CI = 1.13-3.18) ### Page 144 #### b. Zonisamide Weight loss and anorexia were noted as side effects when zonisamide was used to treat epilepsy in participants with binge eating disorder and obesity. A randomized, double-blind, placebo- controlled trial concluded a mean weight loss of 4.8kg from baseline to study endpoint in the intent-to-treat group, with weight loss of 8.9kg in participants completing the 16 weeks of treatment, and a significant reduction in binge frequency. Patients started at zonisamide 100mg/day for 7 days, then increased as tolerated to a max dose of 600mg/day. The mean daily dose at the last evaluation was 436mg. Adverse effects were more common in the zonisamide treatment group (leading to discontinuation of therapy) compared to placebo, although not statistically significant.(373) A 1-year randomized, double-blind, placebo-controlled trial showed zonisamide 400mg/day moderately enhanced weight loss with diet and lifestyle counseling, with an increase in gastrointestinal, nervous system, and psychiatric adverse events compared to placebo.(374) Amean weight loss of 7.3kg was found in patients taking zonisamide 400mg/day, and a mean weight loss of 4kg for zonisamide 200mg/day. Zonisamide 400mg/day resulted in 3.3kg of greater weight loss than diet and lifestyle intervention alone, while the 200mg/day dose was found to not be effective. Although zonisamide 400mg/day showed moderate efficacy in a similar magnitude of weight loss seen with orlistat and lorcaserin, mood changes and memory problems occurred at a higher frequency than with placebo. #### c. Metformin Modest weight loss has been well-documented with the use of metformin when used to treat patients with DM, pre-diabetes, metabolic syndrome, and polycystic ovary syndrome (PCOS).(120,375-379) It has also been shown to cause weight loss in patients without DM withantipsychotic-induced weight gain.(380) In patients with T2DM, reductions have persisted for tenyears or more, and the most important influence on both weight loss and maintenance is adherence to metformin therapy.(381) Additional data are needed for the use of metformin forweight loss in patients without the aforementioned conditions.(382) Metformin is generally safe,though the risk of lactic acidosis (boxed warning) must be considered, particularly in patients with dehydration, renal insufficiency, or those receiving acute loads of intravenous contrast media for radiologic procedures. According to the product information, GI side effects are one of the most commonly reported adverse events in patients treated with metformin; measures may be taken to minimize these side effects (e.g., take the dose with a meal; use of the extended-release formulation). #### d. Glucagon-Like Peptide-1 Receptor Containing Agonists indicated for Type-2 Diabetes Mellitus management (dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide) A Cochrane review of 17 RCTs involving 6,899 participants and typically lasting 26 weeks showed weight loss of 2.87 kg and 3.24 kg for exenatide and liraglutide (3 mg dose FDA-approved for weight loss), respectively, in patients with T2DM.(383) Additional data on weight loss are availablein an open-label trial designed to evaluate the effect of treatment on HbA1c in patients with T2DM; the mean baseline BMI of patients in this trial was approximately 34 kg/m2, with a weight loss of 5.6 kg with semaglutide and 1.9 kg with exenatide.(384) A Phase 2 trial with semaglutide inpatients with obesity (without DM) compared to liraglutide 3.0 mg daily and placebo has also been ### Page 145 published with positive results. Weight loss was significantly higher in all semaglutide groups versus placebo, and significantly higher compared to 3.0 mg liraglutide at doses of semaglutide of 0.2 mg per day or more.(385) Nausea is common with these agents and tends to subside withcontinuation of therapy. Clinically, it is feasible to dose escalate more slowly to an eventual goal dose if a patient reports GI intolerance, given multi-click pen formulations. The risk of inducing pancreatitis is a concern, though in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial including a total of 9,340 patients with T2DM, there was a higher absolute number of patients in the placebo arm with acute pancreatitis (23, 0.5%, 1.7 events/1000 patient-years of observation [PYO]) than in the treatment arm with liraglutide (18, 0.4%, 1.1 events/1000 PYO).(386) Due to rat and mouse data with increased C-cell tumors in those animals, there is a boxed warning of thyroid C-cell (medullary) tumor risk, and GLP-1 agonists are contraindicated in patients with a personal or family history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia type 2 (MEN2). #### e. Sodium-Glucose Cotransporter 2 Inhibitors (empagliflozin, dapagliflozin, canagliflozin, ertugliflozin) As a class, sodium-glucose cotransporter 2 inhibitors cause glucosuria by inhibiting the reabsorption of the filtered glucose load in the proximal tubule. In this fashion, calories are lost through the urine. This can result in some weight loss in patients with T2DM in whom this class of agents has current FDA approval for use. In trials of 12 – 52 weeks duration, with two of these agents (dapagliflozin, canagliflozin), weight loss of 2 – 3 kg was seen.(387) In a meta-analysis oftrials of one to two years duration, SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) showed an MD at two years compared to placebo of –2.99 kg, 95% CI: –3.64 to –2.34. Warnings and precautions for the SGLT2 inhibitors include ketoacidosis, genital mycotic infections, and rare cases of necrotizing fasciitis.(388,389) There remains a boxed warning for theuse of canagliflozin in the setting of foot ulcers or amputations. Renal function should be monitored with use. #### f. Bupropion Bupropion, as monotherapy, has been noted to cause weight loss when used in patients with depression or those seeking to abstain from tobacco.(390) In studies of patients taking dailybupropion combined with naltrexone, there was a weight loss of approximately 5 kg more with treatment compared to those receiving a placebo.(391-393) The combination of naltrexonesustained-release/bupropion sustained-release is now FDA-approved for long-term weight management. Bupropion has a boxed warning for suicidality and is contraindicated in patients with a seizure disorder, bulimia, or anorexia. (390) #### g. Naltrexone Monotherapy As a μ-opioid receptor antagonist, naltrexone is commonly used for the treatment of opioid and alcohol use disorders.(394) It is conjectured that naltrexone reduces food consumption throughthe blockage of β-endorphin action at the μ-opioid receptor as well as preventing autoinhibition of pro-opiomelanocortin neurons, thus influencing the neurological reward pathways in the brain. In a small proof-of-concept study, N=11, Tek et al. (2014)(395) found that compared to placebopatients, patients in the naltrexone 25mg daily arm had significant weight loss (-3.4 kg) compared with weight gain (+1.37 kg) in the placebo group. Indications for naltrexone use include moderate to severe alcohol use disorder and moderate to severe opioid use disorder. It is recommended to ### Page 146 avoid use in patients with acute hepatitis, liver enzymes greater than 3 times the upper limit of normal, or liver failure. #### h. Acarbose Acarbose is a competitive inhibitor of pancreatic alpha-amylase and intestinal brush border alpha- glucosidases. It inhibits the metabolism of sucrose to glucose and fructose. It has an FDA indication for the treatment of type 2 diabetes mellitus, initiated at 25 mg 3 times daily with the first bite of each main meal (or starting with 1 meal with gradual up titration), maximum dose for less than 60 kg is 50 mg 3 times per day, and a greater than 60 kg is 100 mg 3 times a day. Consider liver function testing at full dosing. Contraindicated in patients with cirrhosis. Off-label use for the treatment of postprandial hyperinsulinemic hypoglycemia after gastric bypass. Zhang et al. (2020)(396) performed a systematic review network meta-analysis of randomized control trialscomparing acarbose with dipeptidyl peptidase-4 inhibitors, found comparable glucose lowering butsuperior weight loss with acarbose use (MD −1.23 kg, −2.08 to −0.33). More adverse events were seen with acarbose use initially, with similar event numbers with longer treatment. More frequent dosing requirements with each meal could be a hindrance to use, however. #### i. Pramlintide Pramlintide is a synthetic analog of the human peptide hormone amylin that is co-secreted by pancreatic beta cells in response to eating food. Amylin in the body reduces postprandial hyperglycemia by causing some delay in gastric emptying, lowering glucagon release, and causing appetite suppression at central appetite centers. In a 4-month RCT of N=411(397),patients who had obesity (with an 8 month single blind extension) were randomized to different doses of pramlintide vs. placebo. At the end of the randomized 4-month portion, weight loss from baseline in the pramlintide arms ranged from 3.8 ± 0.7 to 6.1 ± 0.8 kg vs. 2.8 ± 0.8 kg with placebo. At 12 months, weight regain occurred in the placebo group but was maintained inpatients on the higher doses of pramlintide of 120 μg t.i.d. and 360 μg b.i.d. Weight loss was notmaintained in the lower 120-μg b.i.d. group. While not approved for the indication of weight management, pramlintide is FDA-approved for the treatment of both type 1 and type 2 diabetes mellitus. Per package insert, dosing recommendations are to start SUBQ: 15 mcg immediately prior to major meals and to reduce mealtime insulin (including premixed insulin) dose by 50% when starting pramlintide. Side effects include nausea and hypoglycemia when combined with insulin therapy. #### j. Amphetamines/Stimulants (e.g., mixed amphetamine salts, lisdexamfetamine, methylphenidate) Weight loss in children prescribed stimulants is considered a treatment-limiting adverse event. No studies have been published with weight loss as a desired outcome in adults with obesity. All of these medications have concerns and/or boxed warnings for abuse/dependence and CV/central nervous system side effects. Vyvanse has FDA approval for binge eating disorder.(398) #### k. Cyanocobalamin (Vitamin B-12) Vitamin B-12 has a very limited role in promoting weight loss. Based on theoretical extrapolation of the actions of vitamin B-12 at the cellular level, it is sometimes used to promote weight loss. There are no studies evaluating weight loss with Vitamin B-12 injections, tablets, sublingual pills, or drinks. Conversely, B-12 deficiency has been associated with weight loss, particularly after ### Page 147 bariatric surgical procedures, and can lead to permanent nerve damage if left untreated.(399) Noweight loss should be anticipated as a result of the use of exogenous vitamin B-12. Risks of injection site reaction might be anticipated if that route is chosen. In patients with normal renal function, a hypervitaminosis state is unlikely. #### l. Testosterone Replacement Therapy Testosterone replacement therapy has been advocated to achieve weight loss in hypogonadal men with obesity.(400) However, two SRs showed that adipose tissue decreased by only 1.6 kgwhile lean body mass increased by 1.6 kg, with no overall difference in body weight versus placebo.(401,402) Similarly, testosterone supplementation in eugonadal men (total testosterone350-400 ng/dL or higher) leads to no improvement in weight loss. There also remains significant controversy and mixed results regarding the cardiovascular effects of testosterone therapy in general.(403-405) This is an area requiring further review.(406) #### m. Estradiol Replacement Therapy On average, women gain about 1.5 lbs. per year during midlife (between the ages of 40 and 59), independent of initial body size or race/ethnicity, though roughly 20% may gain 10 pounds or more.(407,408) Controversy remains regarding the contributions of aging, with loss of leanmuscle mass resulting in a decrease in resting metabolic rate and subtle decreases in physical activity with age, vs. the estrogen deprivation of menopause. Because aging results in a decrease in both basal and total energy expenditure, basal metabolic rate calculators are age dependent.(409,410) Midlife women are exposed to several unique and interrelated influencesthat promote weight gain: estrogen deprivation, mood disorders, and sleep disturbances.(411)With the loss of estrogen, there is preferential deposition in visceral fat due to estrogen receptors on adipocytes.(412) Estrogen is weight-neutral but improves body fat redistribution.(413)However, despite its favorable influence on body fat distribution menopausal hormone therapy cannot be specifically recommended as a treatment for the sole indication of central obesity in midlife women as it is not FDA-approved for that specific purpose and may carry a non-zero thromboembolic risk, risk for breast cancer, hypertriglyceridemia, and must be combined with progesterone, an anabolic hormone associated with weight gain, in the presence of a uterus to avoid uterine dysplasia. Current indications for the use of estradiol include, but are not limited to, genitourinary and vasomotor symptoms associated with menopause for patients under the age of 60 or within 10 years of menopause. Contraindications to use include breast cancer. Caution is encouraged in patients with hypertriglyceridemia, risk factors for venous thromboembolic disease, active gallbladder disease, and/or migraine headache with aura. While the ovaries stop producing estradiol, they continue to produce androgens, and levels of sex hormone-binding globulin (SHBG) fall, leading to higher levels of circulating free androgens. These changes are linked to a higher risk of metabolic diseases, type 2 diabetes, and cardiovascular disease, as cholesterol levels shift unfavorably with rising low-density lipoprotein (LDL) and falling high-density lipoprotein (HDL) levels. Effective treatment strategies should combine culturally sensitive lifestyle and behavioral interventions with consideration of pharmacologic and surgical options when appropriate. Menopause hormone therapy (MHT), while not a weight-loss treatment, can improve symptoms like hot flashes, sleep disturbances, and quality of life. ### Page 148 #### n. Thyroid Hormones Several small studies have evaluated the association between weight loss and the use of levothyroxine and liothyronine replacement in hypothyroid patients.(414) Normalization of thehypothyroid state is associated with small losses of weight (typically less than 1 kg), which are not durable beyond 12 – 24 months. Normalization of the hyperthyroid state is associated with a weight gain of approximately 7 kg. Treatment of euthyroid patients to hyperthyroid levels has not been reported outside of control groups in early-phase clinical trials. The risks associated with hyperthyroidism, particularly cardiac, ocular, bone, and neuropsychiatric, make intentional creation of a hyperthyroid state highly inadvisable for weight loss. Hyperthyroidism (e.g., Graves’disease) is a condition that requires treatment to avoid negative health consequences. Iatrogenic hyperthyroidism accrues significant harm. #### o. Human Chorionic Gonadotropin Human chorionic gonadotropin (HCG) has no role in weight loss therapy, is ineffective, and has serious safety concerns. A meta-analysis published in 1995 reviewed the use of intramuscular HCG in 24 studies to include 14 RCTs.(415) The authors concluded that HCG was no moreeffective than a placebo or diet alone for weight loss, fat redistribution, or a sense of well-being. Since 1995, there have been no further trials evaluating intramuscular HCG. To date, there are no studies demonstrating the efficacy of HCG drops, pellets, lozenges, or HCG injections (in the absence of severe calorie restriction) over placebo or alternate therapy. Serious adverse events, including deep vein thrombosis and pulmonary embolism (PE), have been reported.(416) ### Page 149 # Appendix K: Metabolic/Bariatric Surgery ## A. Background Metabolic/bariatric surgery (MBS) is one of the most common abdominal operations performed, paralleling the persistent prevalence of obesity in the U.S. and globally. It has been shown to be the most effective and durable treatment for severe obesity. Advances in minimally invasive surgical techniques, surgical instrumentation, and quality improvement and accreditation programs (e.g., American College of Surgeons and American Society of Metabolic and Bariatric Surgery) have led to significant reductions in morbidity and mortality and increased public acceptance of these procedures. Since the National Institutes of Health (NIH) consensus statement on gastrointestinal surgery forsevere obesity in 1991, the accepted indications for MBS included: patients with a BMI ≥40 kg/m2who have failed to achieve significant weight loss by non-surgical means and are fit for surgery, or those with an obesity-related comorbidity and BMI ≥35 kg/m2.(417) Recently, however, theAmerican Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) updated the indications for MBS in a joint statement to better reflect accumulated knowledge of obesity and MBS and reflect modern practice.(418) This included the recommendation for MBS for individuals with a BMI>35 kg/m2regardless of comorbidity status, and evidence to support the option of MBS in conjunction with a comprehensive lifestyle intervention, for patients with DM or other metabolic disease and a BMI≥30 kg/m2. ## B. Outcomes Significant and durable weight loss has been shown in multiple studies. Evidence from observational and experimental studies consistently shows significant absolute and excess weight loss among adults with obesity, persisting 5, 10, and >10 years after surgical intervention.(255,419-425) Evidence from several randomized clinical trials demonstrates thatMBS significantly improves systolic blood pressure, HbA1c, fasting blood glucose, HDL cholesterol, and triglycerides, and reduces medication requirements, compared with non-surgical interventions, variably at 1 – 12 years follow-up.(244,426-430) Furthermore, multiple studiesdemonstrated a survival benefit in different populations with obesity undergoing MBS.(431-434)Overall cancer risk is also reduced in the population with Class 2 or Class 3 obesity after MBS compared with the population with Class 2 or Class 3 obesity that does not undergo MBS.(49,435) In addition, evidence from observational studies suggests that MBS significantlyreduces the incidence of hirsutism, menstrual irregularity, and infertility in women with PCOS and obesity at one year and longer follow-up.(436) Surgery in older patients is associated withincreased morbidity, especially in the presence of frailty. Nonetheless, MBS has been shown to be safe and effective in carefully selected septuagenarians.(437-439). Weight regain can occur afterMBS, as with any weight loss modality, highlighting the chronicity of the disease of obesity. A median weight regain of 9.5% of the maximum weight lost has been reported after 1 year.(440) ### Page 150 ## C. Preoperative Optimization Irrespective of surgical approach, MBS represents a major abdominal surgical procedure with a target population that often has multiple comorbid conditions. Yet, perioperative mortality and overall major morbidity rates are low (<0.1% and <4%, respectively).(427,441-444) Nonetheless,all patients considering surgical intervention should undergo a multidisciplinary preoperative evaluation, with particular attention to cardiopulmonary risk factors, psychosocial barriers, and prehabilitation.(445) As with all surgical procedures, a complete history and physical is required, and the preoperative evaluation should include a review of the screening and assessment elements noted inAppendixO. This includes identification of problematic maladaptive eating patterns that may require furtherassessment or management. Screening for sleep apnea should be considered in all patients with Class 3 obesity, and severe shortness of breath requires a formal assessment for sleep apnea and cardiopulmonary function to identify any potential contraindications to surgery or correctable health issues that could be optimized before surgery.(445,446) Any biliary symptoms should beevaluated with ultrasonography.(447) Patients who smoke should be encouraged to quit andabstain from smoking due to its deleterious effects on pulmonary function and wound healing, especially those undergoing surgery with a gastrointestinal anastomosis. Patients who have active, untreated addictions to drugs or alcohol should not be referred for MBS.(448) Patients considering MBS should be concomitantly enrolled in an integrated comprehensive lifestyle intervention program, both prior to and after the surgical procedure, to provide ongoing guidance and support. The support includes counseling concerning dietary regimen, appropriate physical activity, behavioral treatment, and social support. Adherence to lifestyle changes is essential to long-term and sustained metabolic improvement. Patients should receive preoperative nutritional counseling to ensure they understand postoperative dietary requirements and the need for lifestyle alteration. MBS support groups often facilitate this education both pre-operatively as well as postoperatively. In addition, lifelong medical surveillance after MBS should include monitoring for changes in the status of chronic health conditions and procedure-specific complications such as nutritional deficiencies.(449) Numerous insurance companies mandate enrollment in a structured weight-loss program for a prescribed period of time before patients can be considered for these procedures. There is conflicting evidence as to the benefit of such an approach, and it has been condemned by the American Society of Metabolic and Bariatric Surgery as a barrier to receiving effective health care.(419) The majority of third-party payers and >80% of bariatric programs in the U.S. requirepre-surgical psycho-social evaluations for patients seeking MBS. Psychosocial factors have significant potential to affect long-term outcomes of bariatric procedures, including emotional adjustment, adherence to recommended postoperative lifestyle regimens, weight-loss outcomes, and comorbidity improvement and/or resolution. The evaluating provider plays several important roles in the multidisciplinary treatment of the bariatric patient. Central among these is the role of identifying factors that may pose challenges to optimal surgical outcome and providing recommendations to the patient and bariatric team on how to address these issues.(450) ASMBSand IFSO acknowledge that individuals seeking MBS may benefit from consultation with a multidisciplinary team to help identify and potentially treat modifiable risk factors.(418) ### Page 151 ## D. Potential Contraindications There are few absolute contraindications to MBS, and consultation with the bariatric surgeon should be performed to thoroughly review past medical and surgical history. Relative contraindications that are supported by expert consensus include severe heart failure, unstable coronary artery disease, severe coagulopathies, severe chronic obstructive pulmonary disease (COPD)/end-stage lung disease, active peptic ulcer disease, active cancer treatment, portal hypertension/advanced liver disease, active alcohol/substance abuse, and impaired intellectual capacity/inability to follow pre- and postoperative instructions.(451,452) Expert consensus alsostates that pregnancy is not recommended during the rapid weight-loss phase after MBS; therefore, counseling and follow-up regarding contraception and delay of pregnancy during this period are important.(453,454) ## E. Operations ![Roux-en-Y Gastric $RYGB$ illustration ]() ![Sleeve Gastrectomy $SG$ illustration]() ![Biliopancreatic Diversion with a Duodenal Switch $BPD-DS$ illustration]() Roux-en-Y Gastric (RYGB) Biliopancreatic Diversion with a Duodenal Switch (BPD-DS) Sleeve Gastrectomy (SG) MBS is increasingly recognized as having significant beneficial neurohormonal effects on the regulation of energy balance and hunger control.(456) These effects contribute to weight lossand positive metabolic changes. All operations are preferentially performed using minimally invasive techniques (laparoscopic or robotic). ### a. Roux-en-Y Gastric Bypass Roux-en-Y gastric bypass involves creating a small gastric pouch and a Roux-en-Y reconstruction of the small intestine. An approximately 30 mL gastric pouch is constructed and empties into a Roux limb of jejunum through a gastrojejunostomy. A variable distance downstream from this anastomosis (~100-150 cm), another anastomosis (jejunojejunostomy) is created with the ### Page 152 biliopancreatic limb to form a “common channel” that then proceeds normally to the ileum and empties into the cecum.(457-459) ### b. Sleeve Gastrectomy The sleeve gastrectomy is the most commonly performed MBS procedure in the U.S. and globally.(460) Its origins began as a component of Scopinaro’s biliopancreatic diversion (BPD)with a duodenal switch (DS).(457,461-463) The procedure involves creating a ‘sleeve’ of the stomach by removing 75 – 80% of the volume of the stomach by excising the greater curvature of the stomach, re-shaping the stomach into abanana or “sleeve” shaped organ. Resection starts approximately 4 – 6 cm proximal to the pylorus and progresses close to the gastric cardia to preserve the lesser curvature. It is usually fashioned over a 36-40 French bougie. Studies suggest that medium- and long-term weight loss and metabolic improvement after sleeve gastrectomy are similar to gastric bypass.(244,427,430,461,464,465) Worsening or denovo gastroesophageal reflux disease (GERD) is a risk of sleeve gastrectomy, although some patients with GERD report improvement or remission.(466) ### c. Biliopancreatic Diversion with Duodenal Switch BPD with DS entails an SG and duodenal bypass affected by a proximal Roux-en-Y duodenojejunostomy. This operation has the greatest malabsorptive effect and produces the greatest weight loss and rates of T2DM resolution, but also has a higher risk of significant surgical and metabolic morbidity.(424,467) Technical complexity and long-term nutritional deficiencieshave limited its acceptance and popularity in the U.S. ASMBS estimates from 2022 are that BPD comprised only 2.2% of bariatric procedures performed.(468) ### d. Other Operations Single anastomosis duodenoileostomy with sleeve (SADI-S) is performed by creating a sleeve gastrectomy, an end-to-side duodenoileostomy to a loop of ileum, leaving a blind end of the hepatobiliary limb. This, like BPD-DS, is a highly malabsorptive procedure that produces significant weight loss and excellent metabolic improvement. This can be performed following a sleeve gastrectomy. Like BPD, the SADI-S is associated with greater early postoperative morbidity compared with RYGB and SG. The risk of nutritional deficiency is similar to BPD.(469) One anastomosis gastric bypass (OAGB) is a common operation outside the United States. It consists of creating a vertically oriented gastric pouch based on the lesser curvature, and a gastrojejunostomy to a loop of jejunum 150-250 cm from the ligament of Treitz. Durable weight loss outcomes and improvement of comorbidities have been demonstrated. Malnutrition and bile reflux remain a concern.(470,471) ## F. Mortality Risk Mortality risk after primary MBS is low, compares favorably with other abdominal surgeries, and varies by surgical procedure. A systematic review and meta-analysis including more than 3,650,000 patients showed an overall perioperative mortality risk of 0.08%.(444) By operation ### Page 153 type, the mortality risk after SG is 0.05%, after RYGB 0.09%, and 0.41% after BPD-DS. Risk factors for one-year mortality included older age, male sex, higher BMI, presence of 30-day leak, 30-day PE, and 30-day hemorrhage.(442,472-474) Revisional MBS carries a higher risk ofmortality and morbidity. ## G. Morbidity Risk Overall complication rates are low and have decreased over time from 4.6% (2006) to 3.0% (2013).(467) The type of procedure performed and surgical approach are associated with therisk of morbidity. A one-year analysis of 4,756 patients from the American College of Surgeons' National Surgical Quality Improvement Program (ACS NSQIP) database showed that laparoscopic adjustable gastric banding (LAGB) carried a lower 30-day rate of major complications compared with laparoscopic RYGB (1.0% versus 3.3%), return visits to the operating room (0.9% versus 3.6%), and shorter postoperative stay (median one versus two days).(475) Similarly, from the same database, open RYGB had a higher morbidity (7.4%) thanthe laparoscopic approach (3.4%). BPD with DS had the highest rate of morbidity and mortality, paralleling its increased technical difficulty.(476) ## H. Suicide/Self-harm Risk A review of observational studies suggested an increased risk of suicide after bariatric surgery. Compared with age, sex, and BMI-matched controls, individuals who underwent bariatric surgery had an odds ratio for suicide of 3.8 (95% CI, 2.19-6.59), based on 5 case-control studies.(477)However, the findings by others suggest that the rate of suicide after bariatric surgery may be lower than the global rate in the general population.(478) Lifetime suicide attempt rates may notbe significantly different between the population with and without bariatric surgery.(479). A studyspecific to the VA population demonstrated an increased risk of suicidal ideation (adjusted hazard ratio (aHR) = 1.21, 95% CI:1.03-1.41), and an increased risk of suicide attempt (aHR=1.62, 95% CI:1.22-2.15).(480) At the same time, studies of short- and medium-term outcomes of MBS demonstrated lower rates of depression after bariatric surgery; but it is unclear whether these are sustained long-term or may worsen after 4-9 years.(481) Nonetheless, findings underscore the importance of a pre-operative psychosocial evaluation of individuals considering MBS, as well as post-operative follow-up.(445,450) Table K-1. Potential Complications Associated with Surgical Procedures ### Page 154 a Varies, based on operation performed b Vitamins B1, B12, A, D, E, K, Folate, Iron, Calcium, Zinc, Copper Abbreviations: BPD-DS: Biliopancreatic Diversion with Duodenal Switch; RYGB: Roux-en-Y Gastric Bypass; SG: Sleeve Gastrectomy ## I. Nutritional Concerns It is recommended that all patients receive daily [bariatric] multivitamin and be monitored routinely by an experienced team to detect nutritional deficiencies (seeTable K-2). The AmericanAssociation of Clinical Endocrinologists, American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, the Obesity Medicine Association, and the American Society of Anesthesiologists jointly published clinical practice guidelines for the nutritional and metabolic support of patients undergoing MBS.(449) Susceptibility to nutritionaldeficiencies varies between the different bariatric procedures. Individuals undergoing RYGB or BPD-DS are at greater risk for micronutrient and macronutrient deficiency. A low-carbohydrate diet can avoid dumping syndrome. Non-metabolic surgeries can also result in nutritional deficiencies since the volume of food intake is markedly reduced. Bariatric-specific multivitamins are recommended long-term. Furthermore, it is recommended that postoperative patients receive an average of 60 – 120 g of protein daily to avoid protein malnutrition.(449,492) Several nutritional deficiencies are common, and supplementation at higher than the usual recommended daily dose may be required. Table K-2. Example of Post-Surgical Schedule for Clinical/Biochemical Monitoring(449) ### Page 155 X: Indicates the suggested schedule for laboratory monitoring after metabolic/bariatric surgery +/-: Recommended for high-risk patients, including those with excessive weight loss *24-h urinary calcium excretion measurement at 6 months and annually for BPD-DS **Selectively for symptomatic patients or patients at increased risk for deficiency ***Continue annually for patients with ongoing weight loss or increased risk ### a. Recommended Post-metabolic/Bariatric Surgery Nutritional Supplementation and Medications (493) - 1. Daily (lifelong) multivitamin (bariatric/pre-natal) with the following requirements: - • Thiamine (B1) 50 – 100 mg - • Cobalamin (B12) 350 – 1,000 ug (if duodenum bypassed then recommend 1,000 ug sublingual or parenteral (IM/SQ) administration to maintain normal levels - • Folate 400 – 800 ug (800 – 1,000 ug in women of child-bearing age) - • Iron 18 mg males/45 – 60 mg elemental iron in menstruating females or with duodenal bypass - • Calcium 1,200 – 1,500 mg/d - • Vitamin D (D3) 3,000 IU/d - • Vitamin A 5,000 – 10,000 IU/d - • Vitamin E 15 mg/d - • Vitamin K 90 – 120 ug/d - • Zinc 100 – 200% RDA (8 – 22 mg/d) - • Copper 100 – 200% RDA ### Page 156 - 2. Ursodiol 300 mg twice a day for six months (if gallbladder present without stones) for gallstone prophylaxis during acute weight loss - 3. Chemical venous thromboembolism prophylaxis – no clear consensus on dosage or postoperative length of treatment - 4. Proton Pump Inhibitors for RYGB/BPD with DS to prevent marginal ulceration. Not indicated for SG unless the development of symptomatic reflux. - 5. Avoidance of ALL potential ulcerogenic medications (i.e., NSAIDs/acetylsalicylic acid) - 6. Diabetes medications will likely stop or at least substantially reduce after surgery - 7. Weight-based medication doses will likely decrease over time All bariatric procedures can lead to deficiencies in iron, vitamin B12, folate, and calcium during subsequent pregnancies. These deficiencies can result in maternal complications, such as severe anemia, and in fetal complications, including neural tube defects, intrauterine growth restriction, and failure to thrive. Nutrient supplementation following metabolic/bariatric surgery and close supervision before, during, and after pregnancy can help prevent nutrition-related complications and improve maternal and fetal health. Therefore, women who have undergone weight loss surgery and subsequently become pregnant need to receive intensive nutritional follow-up from providers with expertise in clinical nutrition. ### Page 157 # Appendix L: Specific Behavioral Strategies Featured in Comprehensive Lifestyle Interventions ## A. Goal Setting Goal setting involves setting realistic, specific goals for behavior change. The goal includes the specific action to be taken and when, where, how, how long, and how often the individual will engage in that behavior. Writing down or electronically recording the goal and keeping a record of progress with self-monitoring helps to monitor progress toward goals that might be modified as goals are attained. Attaining goals motivates and reinforces continued adherence to changing behaviors. An example of a behavioral goal for increased physical activity is, “I willwalk around the block for 20 minutes at a brisk pace every day at 11:30 A.M. If it rains, I will do 20 minutes of low-impact aerobics in the living room.” An example of a behavioral goal formaking healthier food choices is, “I will eat at least three servings of non-starchy vegetables perday.” ## B. Self-monitoring Self-monitoring is perhaps the most often employed and the most important behavioral strategy. This involves recording all instances of the target behaviors. For weight management purposes, individuals record all details of food intake, physical activity, and body weight daily. Recording often includes information about times of day and associated thoughts, feelings, places, and events that might affect food intake and physical activity. This record-keeping allows individuals to identify eating and physical activity patterns, cues, measurement of actual food intake, and physical activity. Awareness of these factors promotes the development of specific actions to address unhealthy behaviors. ## C. Stimulus Control or Cue Reduction Stimulus control or cue reduction strategies refer to efforts to change the environmental signals or cues for any specific behavior. It includes both techniques to reduce cues, for example, related to caloric intake and physical inactivity; and to strengthen cues for desired behaviors, for example, healthy eating and physical activity. Examples include removing unhealthy food from sight, eating only at the table rather than in the living room, not watching TV when eating, avoiding fast-food restaurants, having healthy snacks immediately available, placing walking shoes in a convenient spot where they will be noticed, and so on. The overall idea is to eliminate signals for unhealthy eating and substitute cues for helpful weight management behaviors in their place. ## D. Positive Reinforcement Positive reinforcement involves providing rewards for desirable behavior. In the context of weight management, this means offering positive consequences for engaging in healthbehaviors that are consistent with an individual’s weight and health goals. Clinically, reviewing food and activity monitoring logs offers a consistent opportunity to give positive feedback and reinforcement. Individuals may also identify their own rewards for engaging in desired behaviors, e.g., self-praise, buying a new pair of running shoes, starting a garden, or getting a new book from the library. ### Page 158 ## E. Stress Management Stress management is used in the treatment of numerous conditions to reduce felt stress because excess stress can stimulate unhelpful thoughts and behaviors. In weight management, excessive stress may frequently lead to changes to eating patterns to physical activity routines. Stress management includes a wide variety of techniques such as relaxation training, biofeedback training, stimulus control, cognitive restructuring, social support, assertiveness training, problem-solving, and mindfulness and meditation. Taken together, the individual becomes more resistant to becoming overly stressed and more capable of coping with and reducing felt stress when it is noticed. ## F. Problem-solving Problem-solving involves teaching an individual to effectively analyze problems, which might otherwise lead to unhelpful behaviors such as eating past the point of fullness. Once contributing factors are accurately analyzed, possible solutions are considered and evaluated for the pros, cons, and probable outcome of each solution, and a workable solution is agreed upon. ## G. Skill Training Skill training refers to training an individual in those skills that are likely to enhance success. For example, participants in weight management are taught skills in evaluating the caloric content of various foods and in planning to attenuate situations where they may be more likely to make choices that are inconsistent with their health goals. They may be taught skills in eating more slowly, cooking more healthfully, or practicing assertiveness to combat weight bias and stigma. ## H. Social Support Social support is widely acknowledged to improve coping in challenging situations. People receive encouragement, positive reinforcement, emotional empathy and support, and guidance from others. A comforting (and stress-reducing) feeling of “not being alone” comes from being in the presence of others who are in the same difficult situation, as occurs in weight management groups, cancer support groups, and many others. ## I. Cognitive Restructuring Cognitive restructuring is a process whereby individuals are taught to become fully aware of automatic negative thoughts, to evaluate those thoughts, and to then replace them with more realistic, adaptive thoughts. Those thoughts then stimulate more desirable behaviors. Negatively oriented, discouraging, over-reactive, and unrealistic thoughts mediate maladaptive behavior.People are frequently not aware of underlying automatic thoughts such as “I MUST clean my plate!” or “I will NEVER be able to do this!” These thoughts often lead to engaging in undesirable behavior. Cognitive restructuring can be used to identify and modify unhelpful thoughts and attitudes about weight management. Cognitive restructuring may be particularly useful for internalized weight stigma, e.g., “It’s my fault that I have a weight problem” or “People will think I don’t have self-control because of my weight.” ### Page 159 ## J. Relapse Prevention Training Relapse-prevention training helps individuals respond productively to lapses in their efforts to adopt new behaviors or reduce and avoid maladaptive behaviors. Lapses are inevitable during efforts to change any health behavior. However, many people respond negatively to lapses andexperience feelings of guilt or shame, as well as negative thoughts such as “I am a failure!” or “I’ll never be successful at managing my weight!”. Relapse prevention approaches help peopleto reframe lapses as learning opportunities rather than failures and help them to use cognitive restructuring to address negative thinking and problem-solving strategies to both proactively and reactively plan ways of managing situations that lead to lapses. Role-playing and even “planned lapses” are used to help people practice adaptive responses to lapses. ### Page 160 # Appendix M: Assessing Body Composition Table M-1: Modalities of Assessing Body Composition ### Page 161 Legend: - • Accuracy: = Very Low → = Very High - • Cost: = Low → = Very High - • Practicality: = Low → = Very High Note: Sex, age, and ethnicity-specific thresholds for body fat percentage in defining obesity have been proposed for several body composition measurement methods, but there is no universally established or consensus set of cutoffs that have been established for these methods.(494-496) ### Page 162 Abbreviations: ADP: air displacement plethysmography; BIA: bioelectrical impedance analysis; CT: computed tomography; DXA: dual-energy X-ray absorptiometry; FFM: free fat mass; MRI: magnetic resonance imaging; PBF: percent body fat ### Page 163 # Appendix N: Staging and the Classification of Excess Adiposity Clinical staging is commonly used to assess and communicate an individual’s health status anddisease progression. It provides a streamlined, standardized framework to describe disease severity in a clear and concise manner. Similarly, in obesity management, staging enables providers to assess not only the degree of excess adiposity but also the severity of associated comorbidities, functional impairments, and overall health risk and align treatment intensity with disease severity. While BMI has traditionally been used to classify obesity, it does not account for individual differences in fat distribution, metabolic health, or the physical and psychological impact of obesity. In addition to anthropometric measurements, providers should consider the following clinical criteria when determining an individual’s stage of obesity: 1) Medical signs and symptomsof abnormal tissue or organ function; 2) Biomechanical/functional signs or symptoms of age- adjusted limitations of daily activities; 3) Behavioral signs or symptoms, including mood disorders, eating disorders, and reduced quality of life.(497,498) Staging systems such as the Edmonton Obesity Staging System (EOSS)(498) and thecomplications-centric model endorsed by The Obesity Society and the American Association of Clinical Endocrinologists (AACE)(499) offer a more nuanced approach to risk stratification andmanagement than BMI measurement alone. Higher obesity stages are independently associated with increased risk of complications and all- cause mortality, regardless of BMI category. For example, EOSS incorporates comorbid conditions and functional status and has been shown to predict adverse health outcomes and all- cause mortality more accurately than BMI or waist circumference (WC) alone.(500,501) Thesestaging tools help providers identify patients who may benefit from more intensive or early interventions. Obesity staging enhances clinical decision-making, allows for more tailored treatment plans, and facilitates shared decision-making with patients. Ultimately, staging supports a more individualized, risk-based approach to care, aligning treatment intensity with disease severity to improve health outcomes, especially in healthcare systems where rising costs and resource allocation become important. Given the importance of diagnosing and staging, the CPG Workgroup recommends that busy providers use the table below to assist in quickly assessing disease severity and identifying when to initiate or escalate treatment earlier in the care continuum. ### Page 164 Table N-1: Edmonton Obesity Staging System (EOSS)(502) Abbreviations: CAD: coronary artery disease; GERD: gastrointestinal reflux disease; HF: heart failure; HTN: hypertension; MASH: metabolic dysfunction- associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; OA: osteoarthritis; OSA: obstructive sleep apnea; preDM: prediabetes; preHTN: pre-hypertension; T2DM: type 2 diabetes mellitus ### Page 165 # Appendix O: Additional Information for Managing Patients with Overweight and Obesity Caring for patients with overweight and obesity is clinically important. While ongoing research continues to strengthen the empirical foundation for obesity management, the following accepted practices are meant to guide clinical judgment and support consistent, patient-centered care. ## A. Screening and Clinical Assessment for Overweight and Obesity ### a. Screening Assessment of weight and health-related risk involves the consideration of three key measurements: body mass index (BMI), measurement of adiposity, and evaluation of risk factors for diseases and conditions associated with obesity. The BMI calculation is the most commonlyused screening tool in adult populations to determine an individual’s risk of having overweight andobesity. The BMI calculation, despite its limitations, is considered a quick, easy, reliable, reproducible, and scalable population measurement that can be followed over time. It is definedas a person’s weight in kilograms divided by the square of the person’s height in meters (kg/m2). The optimal frequency of BMI measurements has not been evaluated, but it is generally recommended that they occur at least annually.(8,11) Classifications by BMI are listed inTable O-1. Because BMI is an indirect measure of adiposity, it can be influenced by factors like edema and muscular composition. Hence, although BMI measurements remain a useful tool for assessingadiposity at a population level, it has limitations in determining an individual patient’s risk ofadiposity-associated complications. Patients with increased muscle mass leading to a higher weight and consequently a higher BMI may be classified as having overweight or obesity; alternatively, among individuals with decreased lean muscle mass, the low BMI may lead to decreased recognition of their true adiposity and elevated cardiometabolic risk. Additionally, patients of different ages and ethnic backgrounds have different target BMI ranges, making it more difficult for a provider to determine if a patient is at a healthy weight for their height. Clinical obesity requires confirmation of excess adipose tissue. Due to these limitations, additional anthropometric measures are recommended to better assess adiposity. In the context of insufficient evidence to recommend for or against a particular measure of adiposity to manage clinical outcomes in patients with overweight or obesity (seeRecommendation 1), ourWork Group recognizes the importance of individualization when choosing a screening modality that respects patient dignity and promotes a supportive, non-stigmatizing environment. Visceral fat, also known as intra-abdominal fat, is a significant indicator of risk for obesity-related conditions. Measurements of visceral adiposity can vary between anthropometric measurements and body composition imaging modalities.(503) Among these, waistcircumference (WC) is the most practical and cost-effective anthropometric measurement forassessing a patient’s level of abdominal fat and is an indicator of increased disease risk.(504)This is particularly useful for those who have a BMI between 25 kg/m2 and 30 kg/m2, as WC can help identify those with central adiposity who may be at increased risk for cardiometabolic ### Page 166 disorders. For individuals with a BMI ≥35 kg/m², virtually all individuals will already exceedestablished waist circumference thresholds, and measuring a WC is unlikely to add further risk stratification.(449,504) A WC of ≥ 88 cm [≥ 35 in] (>88 cm [>35 in] for women and ≥ 102 cm [≥40 in] for men (seeTable O-2), indicates increased risk of visceral adiposity and developingcardiometabolic complications. For individuals identified under the broad social category of“Asian,” lower thresholds (≥ 80 cm for women and ≥ 90 cm for men; seeTable O-2) are oftenapplied based on epidemiological studies that reported higher cardiometabolic risk at lower levels of adiposity. Clinicians should therefore apply these cutoffs with recognition of their limitations, engage patients in shared discussion about their relevance, and consider complementary, race-neutral approaches such as waist-to-hip ratio or waist-to-height ratio, which may provide more equitable risk assessment across populations.(9,98,494) To ensureaccurate measurement, WC should be assessed with a tape measure placed around the bare abdomen just above the iliac crest. The tape should be snug, but should not compress the skin, and the measurement should be obtained while the patient is standing at the end of normal exhalation. The measurement should be repeated twice.(505) Two variations of the WC assessment are the waist-to-height ratio (WHtR) and the waist-to-hip ratio (WHR). The WHtR is calculated by dividing waist circumference by height. Compared to BMI or WC alone, WHtR has been shown to be a superior screening tool for cardiometabolic risk factors.(494,506,507) Having a WHtR of ≥ 0.5 has significantly greater discriminatory powerfor detecting hypertension, type-2 diabetes, dyslipidemia, metabolic syndrome, and cardiovascular outcomes. The other metric, the WHR, is a useful tool in identifying increased cardiometabolic risk associated with central obesity, especially among those with smaller body frames.(508) Unhealthy values for WHR are defined as ≥0.90 for men and ≥0.85 for women.(43) The introduction of scales that feature bioelectrical impedance analysis (BIA) technology to measure percent body fat in clinical settings may enhance the assessment of overweight and obesity, for both Service members and Veterans. Recent research indicates that bioelectrical impedance analysis (BIA) technology is a reliable method for measuring percent body fat in clinical settings. Clinicians should remain aware of its limitations, particularly regarding hydration status, and ensure standardized protocols are followed to optimize accuracy and clinical utility.(509) Studies have shown that high-frequency direct segmental multifrequency BIA (DSM-BIA) at 500 kHz and 1000 kHz strongly correlates with dual-energy X-ray absorptiometry (DXA), the reference standard for body composition assessment, with no significant increase in accuracy at higher frequencies. Additionally, BIA devices, particularly octopolar and select foot- to-foot models, have demonstrated high reliability and potential utility for tracking body composition over time. While taking into account its limitations, these findings suggest the use of BIA as a practical tool for body composition assessment in military populations, with acceptable accuracy relative to reference standards. (510,511) Techniques such as dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) offer more precise assessments of body composition, including visceral adiposity and lean muscle mass. This may be a consideration in the evaluation, as low lean muscle mass is independently associated with higher cardiovascular and all-cause mortality, and the prevalence of sarcopenia increases with age and comorbidities (348). Despite their growing availability, ### Page 167 these methods are still rarely utilized in routine clinical practice due to factors such as cost, time constraints, and the need for specialized equipment, dedicated space, and trained personnel (seeAppendix M). As the healthcare landscape evolves, integrating these advanced techniquesof adiposity assessment could enhance our understanding of patient health by providing a more comprehensive picture of body fat distribution and its implications for disease risk. In the context of insufficient evidence to recommend for or against a particular measure of adiposity to manage clinical outcomes in patients with overweight or obesity (seeRecommendation 1), our Work Group recognizes the importance of individualization whenchoosing a screening modality that respects patient dignity and promotes a supportive, non- stigmatizing environment. Table O-1: Body Mass Index (BMI) classifications according to the World Health Organization (WHO) standards Abbreviations: BMI: body mass index Table O-2: Common Methods and Diagnostic Cutoffs for Diagnosing Obesity (512,513) ### Page 168 Abbreviations: BIA: bioelectrical impedance analysis; BMI: body mass index; MRI: magnetic resonance imaging; NHANES: National Health and Nutritional Examination Survey; PBF: percent body fat #### b. Obesity-associated Conditions Obesity is linked to numerous chronic health conditions and an increased risk of morbidity. These include various types of cancer, as well as pulmonary, cardiovascular, cerebrovascular, endocrinologic, rheumatologic, gynecologic, urologic, gastrointestinal, neurologic, and psychiatric complications(514-516) Essentially, all organ systems can be affected in some way (seeSidebar ### Page 169 4). The presence of obesity-related comorbidities should increase the urgency and intensity oftreatment strategies aimed at addressing obesity. #### c. Active-Duty Specific Challenges and Operational Readiness Nearly 70% of U.S. Service members have overweight or obesity, and rates have more than doubled over the last decade.(61) This rise threatens military readiness by increasing the risk ofobesity-related conditions and injuries, reducing deployment capability, driving up healthcare costs, and creating challenges in recruitment and retention.(59,66) Occupational factors play a significant role in the rising rates of obesity, particularly among military personnel. Sedentary work, high levels of physical and mental occupational stress, short or irregular sleep patterns, and adverse lifestyle conditions contribute to excess weight gain. Service members are especially vulnerable due to the intense stress of military duties, deployments, and frequent relocations, which are also linked to mental health issues like depression, PTSD, and disinhibited eating. Environmental challenges, such as limited access to healthy food options at home stations, and even more so during deployments or aboard ships, further compound the problem. Environmental challenges, such as limited access to healthy food options during deployments, aboard ships, or on installations with limited health retail or dining options. Food insecurity among some military families, coupled with limited family health literacy and education on nutrition, may further influence dietary behaviors. Addressing these multifactorial influences is essential to implementing effective, evidence-based standards and interventions.(517-519)Obesity in Service members is also associated with reduced physical performance, increased risk of heat stress, sleep apnea, musculoskeletal injuries, and psychological conditions, including anxiety, depression, and substance use disorders.(520-522) Significant challenges, including earlier existing body composition standards, underdiagnosis, lack of access to qualified obesity care, and inconsistent or ineffective weight management programs, may undermine efforts to address obesity. Social stigma can discourage Service members from seeking care, while military appearance regulations may allow commanders to subjectively apply or bypass interventions.(523,524) Lack of transparent data on obesity prevalence and relateddischarges may hinder implementation of effective, evidence-based solutions.(61) Weight loss strategies aimed at operational readiness in the military must focus on achieving and maintaining optimal body composition and physical fitness. DOD Instruction 1308.03, updated 25 June 2025, titled DOD Physical Fitness/Body Composition Program mandates that all Service members maintain readiness through a holistic approach to physical fitness comprising cardiorespiratory endurance, muscular strength and endurance, and healthy body composition tailored to the occupational demands of their specific military specialties.(525) Each branch isallowed to choose from approved body composition assessment methods, including height-weight screening, BMI, waist-to-height ratio, abdominal circumference, or body-fat calculations, provided standards adhere to DOD’s minimum health thresholds. The instruction also requires science- based physical testing and training programs that enhance general health, prevent injury, andensure members can meet “mission-critical operational physical tasks,” with flexibility for evolving training methodologies. ### Page 170 Lifestyle and behavioral modifications remain the foundation of obesity treatment in the DOD. A 2024 meta-analysis of 10 randomized controlled trials in military populations found a statisticallysignificant mean weight loss of −1.84 kg (-4.0 lbs.) with behavioral interventions, though most studies lasted only 3–6 months and had limited follow-up beyond 12 months.(522) These modestresults do not meet clinically significant weight loss, which is generally defined as greater than or equal to 5% reduction in baseline body weight.(9,11,526) Overall, there are rising obesity rates among active-duty Service members (ADSM). Despite TRICARE coverage since 2018, weight management medications are underutilized. A 2024 study of the Military Health System revealed that only 0.44% of eligible ADSM had received a prescription for an obesity medication.(527) Currently, no overarching DOD or DHA instruction onobesity treatment exists. Service-specific policies vary: the Air Force limits prescription duration for obesity medications; the Army prohibits medications used for “anorexic activity” but does not address obesity treatment; and the Navy and Marine Corps have no formal restrictions.(528,529) As with other chronic medical conditions, the evaluation and treatment of overweight and obesity, and consideration of obesity medications, should follow standard clinical care while also taking into account the ADSM military-specific factors. These include, but are not limited to, the Servicemember’s rate or military occupational specialty (MOS), deployment status, medication safety andstorage requirements, potential side effects, duty restrictions, and overall medical readiness. Additionally, the Service member’s readiness for change and ability to adhere to therapy should be assessed to ensure safe and effective treatment. ADSMs who have experienced weight regain, have not achieved sufficient results with intensive lifestyle interventions, or have obesity- related complications may be appropriate candidates for obesity medication therapy. #### d. Clinical Assessment of Patients with Overweight or Obesity An assessment of a patient’s history (see Sidebar 3) identifies the medical, genetic, social, andbehavioral factors that may affect his or her weight and energy balance. Using person-centered, nonjudgmental language, patients should be assessed for factors contributing to obesity, including obesogenic medications that may be being prescribed (see Sidebar 2), comorbid medical and psychiatric conditions (e.g., depression, anxiety, eating disorders, substance abuse), a family history of diabetes and heart disease, dietary patterns and physical activity behaviors (and the potential need for additional education), previous experience with weight management (including clinical interventions as well as self-management), and the patient’s motivation and readiness tocommit to a weight management intervention.(514,515) It is helpful to assess a patient’s currentlevel of physical activity (including activity type, frequency, duration, and intensity) and the presence of sedentary behaviors (e.g., prolonged periods of inactivity). A nutritional evaluation and history may include an assessment of eating behaviors (e.g., frequency of snacking, intake of high-caloric foods and sugar-sweetened beverages, nocturnal eating, and other behaviors that may suggest disordered eating or an eating disorder). A comprehensive nutritional assessment also goes beyond food intake, incorporating environmental and lifestyle factors such as family preferences, social and occupational demands, scheduling challenges, and access to healthy food and cooking resources. Recognizing these influences is essential, as they directly shape the feasibility and sustainability of individualized treatment strategies for obesity. Weight and weight ### Page 171 management history may include the number and types of methods and attempts at weight loss, possible triggers of weight gains and losses, and the range of weight fluctuations. Assessment may identify strengths and resources as well as factors that may impact patient participation in weight management programs. A physical exam, including vital signs, height, weight, calculation of BMI, and incorporating measurements of body fat distribution, such as waist circumference, waist-to-hip ratio, and waist- to-height ratio, should be performed. If readily available and necessary for clinical evaluation, providers can consider the use of additional adiposity measurement tools such as bioimpedance analysis (BIA), air displacement plethysmography (BodPod), etc. Laboratory evaluation plays an important role in the clinical assessment of individuals with overweight or obesity. It can help identify obesity-related comorbidities, screen for secondary causes, guide treatment decisions, and establish a baseline for monitoring progress or treatment effects. Blood tests that evaluate metabolic biomarkers provide critical insight into health status beyond BMI and anthropometric measures. Identifying abnormalities in glucose regulation, lipid profiles, liver function, and inflammatory markers can reveal underlying dysfunction and guide more precise, targeted interventions in obesity treatment and metabolic healing. The specific tests ordered should be tailored to individual risk factors, but commonly include a comprehensive metabolic panel (CMP), hemoglobin A1c, Complete Blood Count (CBC), Thyroid Stimulating Hormone (TSH), and a lipid panel including non-HDL or apo B (note that a post-prandial lipid panel after food intake assesses cardiovascular risk better than a fasting panel).(530,531) FIB-4 scores should be used to evaluatefor MASLD/MASH risk, especially in individuals with prediabetes, diabetes, and any cardiovascular risk factor.(532) Information obtained from this assessment may identifyopportunities to eliminate or reduce obesogenic factors or mitigate the contribution of associatedmedical or psychiatric conditions to the patient’s overweight or obesity. A careful review of patients' medication lists should also be done, as they may reveal medications that cause weight gain that can undermine efforts at maintaining a healthy weight (seeSidebar 2).Reaching out to providers who are prescribing medications that cause weight gain, asking them regarding alternative options that are weight-neutral or possibly promote weight loss, and encouraging patient/provider dialogue is key ([Medications that May Affect Weight](https://www.healthquality.va.gov/guidelines/CD/obesity/MedsEffectsWeightProviderToolFINAL50817Dec2020.pdf)). Theknowledge gathered will be useful when promoting healthy behaviors and engaging in shared decision-making on weight management options. ## B. Counseling Patients Without Overweight and Obesity As noted in theAlgorithm, the CPG Work Group encourages providers to offer guidance ondietary intake and physical activity to patients who have a normal range BMI. This is supported by a USPSTF recommendation that emphasizes that in adults without known cardiovascular disease (CVD) risk factors, behavioral counseling interventions to promote a healthy diet and physical activity are associated with small but statistically significant benefits across various intermediate health outcomes.(533) These outcomes include reductions in blood pressure, low-densitylipoprotein cholesterol levels, and body mass index, as well as improvements in dietary and physical activity behaviors.(534) ### Page 172 The CPG Work Group encourages providers to: 1) encourage patients without overweight and obesity to implement or maintain, as applicable, a healthy weight; 2) discuss strategies for healthy eating, recommended levels of physical activity, consistent and sufficient sleep, and stress management; 3) conduct nutritional counseling focused on prioritizing minimally processed, nutrient-dense whole foods such as vegetables, fruit, lean protein, whole grains, nuts, and dairy products (avoiding those with significant added sugars including high fructose corn syrup);(535)and 4) encourage patients to move more and sit less throughout the day, emphasizing that some physical activity is better than none. For substantial health benefits, adults should do at least 150 minutes per week of moderate-intensity aerobic activity and 2 or more days per week of muscle- strengthening activities of moderate or greater intensity that involve all major muscle groups.(212,536) Brief physical activity counseling by healthcare providers can have a small to moderatepositive effect on increasing physical activity levels and reducing sedentary time.(537) A carefulreview of patients' medication lists should also be done, as they may reveal medications that cause weight gain that can undermine efforts at maintaining a healthy weight (seeSidebar 2).Also, screening for sleep disturbances and stress, and considering referral for sleep medicine or cognitive-behavioral therapy when indicated.(295) ## C. Shared Decision Making to Choose Among Weight Management Options In individuals with overweight or obesity, the clinical team should engage the patient in a shared decision-making process regarding weight management options. Shared decision making (538) isderived from evidence-based principles of health education (539) and health behaviorcounseling.(540,541) It is important to use a person-centered communication style that includesactive listening and nonjudgmental language to elicit individual preferences and beliefs, which is essential for optimizing health outcomes and quality of life.(531,542,543) Strategies for effectively reaching shared understanding are: - • To support patient autonomy, ask permission to discuss weight-related health risks and the potential benefits and concerns of weight loss and/or weight management(543) - • Explore the patient’s understanding, beliefs, experience, and values regarding the healthrisks associated with their weight and the potential impact of weight management on their health and well-being - • If a patient declines to discuss their weight, honor that decision and ask permission to discuss at a future visit - • Share information about potential health risks that are tailored to the patient’sunderstanding, his or her weight, his or her current health status, and the presence of weight-associated conditions - • Emphasize obesity as a chronic disease that requires ongoing attention as well as individualized and comprehensive management - • Provide appropriate amounts of information in a manner that is easy to understand - • Use a “teach-back” method to confirm shared understanding(539,541-544) - - ### Page 173 - - - - - - - - • Review patients’ prior experience with weight management interventions, their perceptions about the benefits of weight loss management, and their values - • Explore what matters to patients about their health and function to align recommendations with their values (e.g., “preventing complications of diabetes will help you to be available to your family, which you said is very important to you”) Ultimately, the process of reaching a shared understanding goes beyond simply educating patients about their conditions and the benefits of weight loss. It is a dialogue that begins withexploring the patients’ perceptions, beliefs, and experiences, and allows for the creation of a plan that is tailored to them. Exploring, accepting (without judgment), and affirming patients’ values andpreferences supports their autonomy, builds trust, and fosters provider-patient partnerships. This, in turn, is associated with increased patient follow-through with health behavior change and participation in recommended treatment.(543,545) ### a. Weight Stigma Applying a patient-centered approach also requires that providers address the impact that weight stigma and bias have on patients’ physical and psychological health, well-being, their willingness to participate in weight management, and their progress with weight management efforts.(546)We suggest offering cognitive behavioral interventions to reduce internalized weight bias and stigma in affected individuals (seeRecommendation 10). Many healthcare providers hold strong,negative attitudes about people with overweight and obesity, and there is evidence that such attitudes may impact the care they provide, further exacerbating negative effects on patient well- being.(546,547) A patient-centered approach that emphasizes provider awareness of theircontributions to stigma and bias, use of person-first language (e.g., using the word obesity as a noun, rather than as an adjective, “people with obesity” instead of “obese patients”), andincreased use of empathy and patient-centered communication skills can enhance the quality of clinical interactions.(546-548) #### b. Motivational Interviewing If an initial assessment of the patient’s motivation indicates they are not ready to commit to a recommended treatment, motivational interviewing techniques can be applied to build motivation and patient engagement. Motivational interviewing is a patient-centered counseling style that involves four key tasks: engaging, focusing, evoking, and planning.(549-551) Engaging strategies,including open-ended questions, active listening, reflections, and empathetic response, builds trust and deepens both patient and clinician understanding of patients’ motivations. Focusing identifies and clarifies the patient's goals and values, respecting their autonomy and negotiating a collaborative agenda. Evoking strategies that elicit “change talk” (e.g., desire, ability, reasons, andneed) using targeted questions, requests for elaboration, and reflections, while also softening“sustain talk” can build motivation. Planning involves developing a concrete action plan that aligns with the patient's readiness and resources and, if the patient is willing, setting SMART goals (Specific, Measurable, Action-oriented, Realistic, and Time-based) (seeTable O-3), and ensuringfollow-up. ### Page 174 Although there is considerable evidence that using motivational interviewing increases the likelihood that a patient will follow through with treatment recommendations across a wide range of health behaviors, there is only limited evidence for the impact of motivational interviewing on follow-through with weight management treatment.(543,552-560) Principles and core strategies ofmotivational interviewing are listed inSidebar 1.(561) A comprehensive lifestyle intervention, asdefined in this CPG, that incorporates the principles of motivational interviewing has the potential to enhance patient engagement and weight management outcomes. Table O-3: SMART Goals for Healthy Weight ### Page 175 #### c. Eliciting a Commitment to Participate in Weight Management and Choosing Among Treatment Options After reaching a shared understanding, the next step is to elicit a commitment from the patient to engage in a recommended evidence-based weight management intervention. This critical step is accomplished by asking an open-ended question. For example, a provider might say, “Given whatwe discussed about the potential benefits of participation in a weight management program, howready are you to commit to treatment?” If the patient expresses a willingness to commit, share theavailable options for engaging in treatment. Guide the patient to choose a treatment that is aligned with their needs and preferences. This step in the process can be initiated by referring the patient to an established comprehensive lifestyle intervention (CLI) (e.g., VHA’s MOVE! WeightManagement Program for Veterans) (562) or a member of the healthcare team (e.g., a dietitian, aclinical pharmacist) who can guide the patient to decide among available treatment options. Referring to a clinician with expertise in obesity may be particularly important for those with complex medical histories and/or concurrent pharmacotherapies that may impact the potential benefits and harms of specific weight management treatment components. Emphasizing the role of CLI in weight management is a key element of the shared decision- making process (see). It is critical for patients and providers to understand thatpharmacotherapy and metabolic/bariatric surgery should always be offered in conjunction with or concurrent to CLI, with these interventions viewed as components of a broader treatment strategy. The process of choosing among specific evidence-based weight management interventions includes: a review of previous experience with weight loss and response to treatments; identification of conditions or factors that increase risk of untoward reactions to elements of treatments (e.g., previous adverse effects from weight loss pharmacotherapy or surgical risks); and further exploration of patient preferences for CLI modality (e.g., group versus individual; telephone versus in-person or video) and preferences regarding concurrent pharmacotherapy or metabolic/bariatric surgery. Dietary approaches should promote a negative energy balance to facilitate weight loss, choosing a diet that the patient feels they can maintain (seeRecommendation 6 andRecommendation 7).In addition to creating a negative energy balance, dietary approaches should account for the hormonal and metabolic effects of food, recognizing that nutrient composition influences insulin, satiety hormones, and other regulators of weight and appetite. Aligning both caloric and hormonal balance supports more effective and sustainable obesity treatment. In terms of physical activity, ### Page 176 encouraging any form of physical activity is beneficial for weight management and overall health outcomes (seeRecommendation 8andRecommendation 9). Consider referral for procedural or surgical intervention evaluation for patients interested in considering those options in combination with CLI. (seeRecommendation 11,Recommendation12, andRecommendation 13). We recommend combining pharmacotherapy with CLI. There is noevidence for or against delaying the initiation of FDA-approved pharmacotherapy when combined with CLI (SeeRecommendation 14). Once a medication is found to be safe and effective for apatient, continuation of the medication is encouraged due to the risk of weight regain after discontinuation and the chronicity of obesity as a disease. Slow tapering of medication, with monitoring of impact, is recommended if the patient prefers to discontinue treatment (seeAppendix J andRecommendations 14-20). #### d. Management of the Patient Not Ready to Engage If the patient is not able to commit to a recommended weight management intervention, the provider might offer educational materials and ask permission to revisit options for weight management in future encounters. Motivational interviewing strategies can be applied at these and subsequent encounters. Providers might also assist the patient to select more limited health behavior goals (e.g., reducing sugar-containing beverages and alcohol, OR adding an extra serving of veggies at dinner, OR increasing physical activity as a first step) that may contribute to future weight management efforts. Using SMART goals is applicable in this scenario (seeTableO-3). ## D. Emphasizing the Role of Comprehensive Lifestyle Intervention Comprehensive lifestyle interventions (CLI) for weight loss and weight maintenance are definedas standardized interventions that combine three critical “lifestyle” components (i.e., behavioral,dietary, and physical activity components) that aim to produce a negative energy balance. Whenever a patient expresses an interest in participating in a CLI, it is important to emphasize several key concepts that apply to all CLIs: - • An “energy deficit” should be reached with a combination of reduced caloric intake and increased physical activity - • A nutritionally adequate diet with adjusted calories should be part of a comprehensive weight management program - • Incremental changes in both dietary changes and physical activity can be supported by using specific behavioral strategies (e.g., goal setting, monitoring, problem solving) to support diet, physical, sleep, and mood management (seeAppendix L) - • Creating SMART goals for changes in dietary patterns and physical activity will support weight loss and weight maintenance (seeTable O-3) - • A short-term initial weight loss goal of 0.5 – 2.0 pounds per week may be achievable with a net caloric deficit of 500-1,000 kcal/day - • Weight management is a lifelong commitment, not a brief episode of treatment - - ### Page 177 - - - - - - - • Obesity is a chronic disease, and CLI alone may not be sufficient for sustainable weight loss for many adults with overweight and obesity. However, CLI remains important for metabolic, biomechanical, and psycho-social health as part of a comprehensive weight management treatment plan - • Weight management strategies that are sustainable over the long term are highly preferred over those that produce short-term weight loss but are unsustainable. ## E. Assessment of Progress Toward Weight Management Goals CLI is foundational to obesity care, not only for promoting weight loss but also for preserving metabolic health, physical function, balance, nutrition, and muscle mass. While change in weight is one measure of progress, providers should help individuals focus on broader markers of success, including improvements in glucose control, blood pressure, lipid profiles, endurance, mobility, mood, energy levels, and quality of life. From the outset, providers should assist patients with identifying realistic expectations and work with them to establish goals that extend beyond weight change. Celebrating non-weight change victories, such as improved sleep, reduced joint pain, improved mood, or lower HbA1c, builds motivation and reinforces long-term engagement. Importantly, individuals must be counseled that weight loss may be easier than maintenance of weight loss, due to adaptive neurohormonal responses that promote weight regain. These biological defenses, such as increased hunger and reduced energy expenditure, make sustained weight loss difficult to maintain with CLI alone (563,564). Observational and retrospectiveanalyses consistently associate higher volumes of physical activity (often >250–300 minutes per week of moderate-intensity exercise) with better long-term weight loss maintenance.(201,565).Thus, it is critical for providers to explain that obesity is a chronic disease requiring long-term, often lifelong management. For many individuals, with moderate to severe obesity or significant complications, pharmacotherapy and/or bariatric procedures or surgery will be important components of an effective treatment plan, concomitant with CLI. We encourage continuation of obesity medication that are impactful and well-tolerated in an effort to reduce the likelihood of weight regain that is often associated with discontinuation. (SeeRecommendation 16). Ongoingpharmacotherapy may be necessary to counterbalance the physiological mechanisms that drive weight regain.(566) Pharmacotherapy and bariatric procedural and surgical interventions supportand enhance the benefits of lifestyle changes and do not replace them. When progress stalls or barriers persist, providers should adjust the treatment plan. This may include intensifying the lifestyle approach, initiating or adjusting obesity medications, or referring for a bariatric procedure or surgery evaluation. Additionally, individuals should be cautioned regarding discontinuing medications in the absence of significant adverse events, as ongoing pharmacotherapy helps counter the physiologic drive to regain weight. Sustained success in obesity care and weight management depends on personalized, progressive, and proactive treatment strategies that integrate lifestyle, medication, and procedural tools to support long-term health and weight stability. To mitigate potential patient frustration, talk with patients and their family members about realistic expectations for weight loss and maintenance, including the importance of long-term follow- ### Page 178 through with lifestyle change, particularly the adoption of a healthy diet, regular physical activity, and other weight management behaviors. ### a. Supporting Long-Term Weight Maintenance Once long-term weight management goals have been achieved, the focus of weight management shifts to the prevention of weight regain. As noted, this goal requires maintenance of dietary and physical activity behaviors and many of the other self-management behaviors that contributed to successful weight loss. Thus, all patients reaching their long-term goals should be offered a maintenance program, ongoing support, and periodic reassessment that may include the need to continue pharmacotherapy or support of post-bariatric procedural or surgical nutritional needs (seeRecommendation 3). # Appendix P: Abbreviation List ### Page 179 ### Page 180 ### Page 181 ### Page 182 ### Page 183 ### Page 184 # References 1. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet. Aug 30 2014;384(9945):755-65. doi:10.1016/s0140-6736(14)60892-8 2. National Cancer Institute. Obesity and Cancer.[https://www.cancer.gov/about-cancer/causes-prevention/risk/obesity/obesity-fact-sheet#:~:text=Compared%20with%20people%20of%20healthy%20weight%2C%20those,risk%20of%20death%20from%20all%20causes%20(2%E2%80%935](https://www.cancer.gov/about-cancer/causes-prevention/risk/obesity/obesity-fact-sheet#:~:text=Compared%20with%20people%20of%20healthy%20weight%2C%20those,risk%20of%20death%20from%20all%20causes%20(2%E2%80%935)). 3. Islami F, Goding Sauer A, Miller KD, et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin. Jan 2018;68(1):31-54. doi:10.3322/caac.21440 4. Evidence Based Practice Work Group Charter (2017). 5. Guyatt GH, Oxman AD, Kunz R, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. Journal of clinical epidemiology. Apr 2011;64(4):395-400. doi:10.1016/j.jclinepi.2010.09.012 6. Ng M, Dai X, Cogen RM, et al. National-level and state-level prevalence of overweight and obesity among children, adolescents, and adults in the USA, 1990–2021, and forecasts up to 2050. The Lancet. 2024;404(10469):2278-2298. doi:10.1016/S0140- 6736(24)01548-4 7. Emmerich SD, Fryar CD, Stierman B, Ogden CL. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021-August 2023. NCHS Data Brief. Sep 2024;(508)doi:10.15620/cdc/159281 8. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. Jun 24 2014;129(25 Suppl 2):S102-38. doi:10.1161/01.cir.0000437739.71477.ee 9. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. Nov 7 2013;doi:10.1016/j.jacc.2013.11.004 10. Rosenbaum M, Foster G. Differential mechanisms affecting weight loss and weight loss maintenance. Nat Metab. Aug 2023;5(8):1266-1274. doi:10.1038/s42255-023-00864-1 11. Garvey WT, Mechanick JI, Brett EM, et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. Jul 2016;22 Suppl 3:1-203. doi:10.4158/ep161365.Gl 12. Heymsfield SB, Wadden TA. Mechanisms, Pathophysiology, and Management of Obesity.N Engl J Med. Apr 13 2017;376(15):1492. doi:10.1056/NEJMc1701944 13. Organization WH. Obesity and overweight. World Health Organization.[https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight#:~:text=Obesity%20and%20overweight%20fact%20sheet%20from%20WHO%20providing,consequences%2C%20double%20burden%20of%20disease%2C%20prevention%2C%20WHO%20response](https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight#:~:text=Obesity%20and%20overweight%20fact%20sheet%20from%20WHO%20providing,consequences%2C%20double%20burden%20of%20disease%2C%20prevention%2C%20WHO%20response). 14. Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the Association of SGLT-2 Inhibitors and Diabetic Ketoacidosis. Endocrine Practice. 2016/06/01/ 2016;22(6):753-762. doi:[https://doi.org/10.4158/EP161292.PS](https://doi.org/10.4158/EP161292.PS) ### Page 185 15. Wharton S, Lau DCW, Vallis M, et al. Obesity in adults: a clinical practice guideline. Cmaj. Aug 4 2020;192(31):E875-e891. doi:10.1503/cmaj.191707 16. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. Oct 27 2011;365(17):1597-604. doi:10.1056/NEJMoa1105816 17. van Baak MA, Mariman ECM. Obesity-induced and weight-loss-induced physiological factors affecting weight regain. Nat Rev Endocrinol. Nov 2023;19(11):655-670. doi:10.1038/s41574-023-00887-4 18. Apovian CA, L. Barenbaum, S. Clinical Management of Obesity, Third Edition. 2025. 19. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report. National Institutes of Health. Obes Res. Sep 1998;6 Suppl 2:51s-209s. 20. Sweatt K, Garvey WT, Martins C. Strengths and Limitations of BMI in the Diagnosis of Obesity: What is the Path Forward? Curr Obes Rep. Sep 2024;13(3):584-595. doi:10.1007/s13679-024-00580-1 21. Prentice AM, Jebb SA. Beyond body mass index. Obes Rev. Aug 2001;2(3):141-7. doi:10.1046/j.1467-789x.2001.00031.x 22. Piqueras P, Ballester A, Durá-Gil JV, Martinez-Hervas S, Redón J, Real JT. Anthropometric Indicators as a Tool for Diagnosis of Obesity and Other Health Risk Factors: A Literature Review. Front Psychol. 2021;12:631179. doi:10.3389/fpsyg.2021.631179 23. Yuen M, Earle R, Kadambi N. A systematic review and evaluation of current evidence reveals 236 obesity-associated disorders. New Orleans: The Obesity Society. 2016; 24. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. Jan 2 2013;309(1):71-82. doi:10.1001/jama.2012.113905 25. Borrell LN, Samuel L. Body mass index categories and mortality risk in U.S. adults: the effect of overweight and obesity on advancing death. Am J Public Health. Mar 2014;104(3):512-9. doi:10.2105/ajph.2013.301597 26. Aune D, Sen A, Prasad M, et al. BMI and all cause mortality: systematic review and non- linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ. May 4 2016;353:i2156. doi:10.1136/bmj.i2156 27. Carr PR, Webb KL, Neumann JT, et al. Associations of body size with all-cause and cause-specific mortality in healthy older adults. Sci Rep. Mar 7 2023;13(1):3799. doi:10.1038/s41598-023-29586-w 28. Obesity, MASLD, & MASH. American Liver Foundation.[https://liverfoundation.org/wp-content/uploads/2024/09/Obesity.MASLD_.MASH-Fact-Sheet_Final.pdf](https://liverfoundation.org/wp-content/uploads/2024/09/Obesity.MASLD_.MASH-Fact-Sheet_Final.pdf) 29. Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. Dec 2 2010;363(23):2211-9. doi:10.1056/NEJMoa1000367 30. Kitahara CM, Flint AJ, Berrington de Gonzalez A, et al. Association between class III obesity (BMI of 40-59 kg/m2) and mortality: a pooled analysis of 20 prospective studies.PLoS Med. Jul 2014;11(7):e1001673. doi:10.1371/journal.pmed.1001673 31. Adams KF, Schatzkin A, Harris TB, et al. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med. Aug 24 2006;355(8):763- 78. doi:10.1056/NEJMoa055643 32. Expert Panel Report: Guidelines (2013) for the management of overweight and obesity in adults. Obesity (Silver Spring). Jul 2014;22 Suppl 2:S41-410. doi:10.1002/oby.20660 33. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. Jun 2004;89(6):2548-56. doi:10.1210/jc.2004-0395 ### Page 186 34. Hajer GR, van Haeften TW, Visseren FL. Adipose tissue dysfunction in obesity, diabetes, and vascular diseases. Eur Heart J. Dec 2008;29(24):2959-71. doi:10.1093/eurheartj/ehn387 35. Garrison RJ, Kannel WB, Stokes J, 3rd, Castelli WP. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med. Mar 1987;16(2):235-51. doi:10.1016/0091-7435(87)90087-9 36. Nyamdorj R, Qiao Q, Söderberg S, et al. Comparison of body mass index with waist circumference, waist-to-hip ratio, and waist-to-stature ratio as a predictor of hypertension incidence in Mauritius. J Hypertens. May 2008;26(5):866-70. doi:10.1097/HJH.0b013e3282f624b7 37. Shihab HM, Meoni LA, Chu AY, et al. Body mass index and risk of incident hypertension over the life course: the Johns Hopkins Precursors Study. Circulation. Dec 18 2012;126(25):2983-9. doi:10.1161/circulationaha.112.117333 38. Nguyen NT, Nguyen XM, Lane J, Wang P. Relationship between obesity and diabetes in a US adult population: findings from the National Health and Nutrition Examination Survey, 1999-2006. Obes Surg. Mar 2011;21(3):351-5. doi:10.1007/s11695-010-0335-4 39. Control CfD, Prevention. National diabetes statistics report, 2017. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services. 2017; 40. Afshin A, Forouzanfar MH, Reitsma MB, et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. Jul 6 2017;377(1):13-27. doi:10.1056/NEJMoa1614362 41. Bays HE, Toth PP, Kris-Etherton PM, et al. Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association. J Clin Lipidol. Jul-Aug 2013;7(4):304-83. doi:10.1016/j.jacl.2013.04.001 42. Prevention CfDCa. Adult Obesity Facts.[https://www.cdc.gov/obesity/data/adult.html](https://www.cdc.gov/obesity/data/adult.html) 43. Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. May 25 2021;143(21):e984-e1010. doi:10.1161/cir.0000000000000973 44. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. Apr 2007;45(4):846-54. doi:10.1002/hep.21496 45. Le P, Tatar M, Dasarathy S, et al. Estimated Burden of Metabolic Dysfunction-Associated Steatotic Liver Disease in US Adults, 2020 to 2050. JAMA Netw Open. Jan 2 2025;8(1):e2454707. doi:10.1001/jamanetworkopen.2024.54707 46. Zhang X, Linden S, Levesley CR, et al. Projected Trends in Metabolic Dysfunction- Associated Steatotic Liver Disease Mortality Through 2040. JAMA Netw Open. Jun 2 2025;8(6):e2516367. doi:10.1001/jamanetworkopen.2025.16367 47. Petrelli F, Cortellini A, Indini A, et al. Association of Obesity With Survival Outcomes in Patients With Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. Mar 1 2021;4(3):e213520. doi:10.1001/jamanetworkopen.2021.3520 48. Luo J, Hendryx M, Manson JE, et al. Intentional Weight Loss and Obesity-Related Cancer Risk. JNCI Cancer Spectr. Dec 2019;3(4):pkz054. doi:10.1093/jncics/pkz054 49. Aminian A, Wilson R, Al-Kurd A, et al. Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity. Jama. Jun 28 2022;327(24):2423-2433. doi:10.1001/jama.2022.9009 50. Vesikansa A, Mehtälä J, Jokelainen J, et al. The association of body mass index with quality of life and working ability: a Finnish population-based study. Qual Life Res. Feb 2022;31(2):413-423. doi:10.1007/s11136-021-02993-0 51. Stephenson J, Smith CM, Kearns B, Haywood A, Bissell P. The association between obesity and quality of life: a retrospective analysis of a large-scale population-based cohort study. BMC Public Health. Nov 3 2021;21(1):1990. doi:10.1186/s12889-021-12009-8 ### Page 187 52. Puhl RM, Heuer CA. The stigma of obesity: a review and update. Obesity (Silver Spring). May 2009;17(5):941-64. doi:10.1038/oby.2008.636 53. Chen F, Su W, Ramasamy A, et al. Ten-year Medicare budget impact of increased coverage for anti-obesity intervention. J Med Econ. Oct 2019;22(10):1096-1104. doi:10.1080/13696998.2019.1652185 54. Ward ZJ, Bleich SN, Long MW, Gortmaker SL. Association of body mass index with health care expenditures in the United States by age and sex. PLoS One. 2021;16(3):e0247307. doi:10.1371/journal.pone.0247307 55. Thorpe KE, Joski PJ. Estimated Reduction in Health Care Spending Associated With Weight Loss in Adults. JAMA Netw Open. Dec 2 2024;7(12):e2449200. doi:10.1001/jamanetworkopen.2024.49200 56. Hammond D, Jones, A., Chriqui, J. F., Chaloupka, F. J. The indirect costs of obesity in the United States: A systematic review and meta-analysis. Preventive Medicine. 2020;109(106203) 57. Department of Defense. FY20 Qualified Military Available Key Findings 58. Ward ZJ, Bleich SN, Cradock AL, et al. Projected U.S. State-Level Prevalence of Adult Obesity and Severe Obesity. N Engl J Med. Dec 19 2019;381(25):2440-2450. doi:10.1056/NEJMsa1909301 59. Defense Health Agency–Public Health (DHA-PH). 2022 Health of the Force.[https://ph.health.mil/Periodical%20Library/2022-Health-of-the-Force-EXSUM.pdf](https://ph.health.mil/Periodical%20Library/2022-Health-of-the-Force-EXSUM.pdf) 60. Beynon S. Once a Pilot, Army Program for Recruits Who Fall Short of Weight, Academic Standards Is Becoming Permanent. Military.com.[https://www.military.com/daily-news/2023/08/30/armys-pre-boot-camp-training-courses-are-here-stay-after-early-success.html](https://www.military.com/daily-news/2023/08/30/armys-pre-boot-camp-training-courses-are-here-stay-after-early-success.html) 61. Project AS. Costs and Consequences: Obesity's Compunding Impact on the Military Health System. 2024.[https://www.americansecurityproject.org/wp-content/uploads/2024/09/Ref-0295-Costs-and-Consequences-Obesitys-Compounding-Impact-on-the-Military-Health-System.pdf](https://www.americansecurityproject.org/wp-content/uploads/2024/09/Ref-0295-Costs-and-Consequences-Obesitys-Compounding-Impact-on-the-Military-Health-System.pdf) 62. Rush T, LeardMann CA, Crum-Cianflone NF. Obesity and associated adverse health outcomes among US military members and veterans: Findings from the millennium cohort study. Obesity (Silver Spring). Jul 2016;24(7):1582-9. doi:10.1002/oby.21513 63. Hruby A, Bulathsinhala L, McKinnon CJ, et al. BMI and Lower Extremity Injury in U.S. Army Soldiers, 2001-2011. American journal of preventive medicine. Jun 2016;50(6):e163- e171. doi:10.1016/j.amepre.2015.10.015 64. Cowan DN, Bedno SA, Urban N, Yi B, Niebuhr DW. Musculoskeletal injuries among overweight army trainees: incidence and health care utilization. Occup Med (Lond). Jun 2011;61(4):247-52. doi:10.1093/occmed/kqr028 65. Centers for Disease Control and Prevention. Unfit to Serve.[https://www.cdc.gov/physicalactivity/resources/unfit-to-serve/index.html](https://www.cdc.gov/physicalactivity/resources/unfit-to-serve/index.html) 66. Callahan E. Understanding and overcoming the challenge of obesity and overweight in the Armed Forces: proceedings of a workshop. National Academies Press; 2019. 67. Dall TM, Zhang Y, Chen YJ, et al. Cost associated with being overweight and with obesity, high alcohol consumption, and tobacco use within the military health system's TRICARE prime-enrolled population. Am J Health Promot. Nov-Dec 2007;22(2):120-39. doi:10.4278/0890-1171-22.2.120 68. Breland JY, Phibbs CS, Hoggatt KJ, et al. The Obesity Epidemic in the Veterans Health Administration: Prevalence Among Key Populations of Women and Men Veterans. J Gen Intern Med. Apr 2017;32(Suppl 1):11-17. doi:10.1007/s11606-016-3962-1 69. Betancourt JA, Granados PS, Pacheco GJ, et al. Exploring Health Outcomes for U.S. Veterans Compared to Non-Veterans from 2003 to 2019. Healthcare (Basel). May 18 2021;9(5)doi:10.3390/healthcare9050604 ### Page 188 70. Blalock DV, Pura JA, Stechuchak KM, et al. BMI Trends for Veterans Up to 10 Years After VA Enrollment Following Military Discharge. J Gen Intern Med. May 2023;38(6):1423- 1430. doi:10.1007/s11606-022-07818-5 71. Betancourt JA, Stigler Granados P, Pacheco GJ, Shanmugam R, Kruse CS, Fulton LV. Obesity and Morbidity Risk in the U.S. Veteran. Healthcare (Basel). Jun 29 2020;8(3)doi:10.3390/healthcare8030191 72. Hachuła M, Kosowski M, Zielańska K, Basiak M, Okopień B. The Impact of VariousMethods of Obesity Treatment on the Quality of Life and Mental Health-A Narrative Review. Int J Environ Res Public Health. Jan 24 2023;20(3)doi:10.3390/ijerph20032122 73. Almandoz JP, Wadden TA, Tewksbury C, et al. Nutritional considerations with antiobesity medications. Obesity (Silver Spring). Sep 2024;32(9):1613-1631. doi:10.1002/oby.24067 74. Wing RR, Lang W, Wadden TA, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes.Diabetes Care. Jul 2011;34(7):1481-6. doi:10.2337/dc10-2415 75. Lazo M, Solga SF, Horska A, et al. Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care. Oct 2010;33(10):2156-63. doi:10.2337/dc10-0856 76. Younossi ZM, Corey KE, Lim JK. AGA Clinical Practice Update on Lifestyle Modification Using Diet and Exercise to Achieve Weight Loss in the Management of Nonalcoholic Fatty Liver Disease: Expert Review. Gastroenterology. Feb 2021;160(3):912-918. doi:10.1053/j.gastro.2020.11.051 77. Haase CL, Lopes S, Olsen AH, Satylganova A, Schnecke V, McEwan P. Weight loss and risk reduction of obesity-related outcomes in 0.5 million people: evidence from a UK primary care database. Int J Obes (Lond). Jun 2021;45(6):1249-1258. doi:10.1038/s41366-021-00788-4 78. MedSci KKF, Schnecke V, Haase CL, et al. Weight change and risk of obesity-related complications: A retrospective population-based cohort study of a UK primary care database. Diabetes Obes Metab. Sep 2023;25(9):2669-2679. doi:10.1111/dom.15154 79. U.S. Department of Veteran Affairs, Department of Defense. Guideline for Guidelines. Veterans Health Administration, Office of Quality & Performance, Evidence Review Subgroup; Revised January 29, 2019. 80. Ransohoff DF, Pignone M, Sox HC. How to decide whether a clinical practice guideline is trustworthy. Jama. Jan 9 2013;309(2):139-40. doi:10.1001/jama.2012.156703 81. Andrews JC, Schunemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation's direction and strength.Journal of clinical epidemiology. Jul 2013;66(7):726-35. doi:10.1016/j.jclinepi.2013.02.003 82. Andrews J, Guyatt G, Oxman AD, et al. GRADE guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. Journal of clinical epidemiology. Jul 2013;66(7):719-25. doi:10.1016/j.jclinepi.2012.03.013 83. Schunemann HJ, Fretheim A, Oxman AD. Improving the use of research evidence in guideline development: 10. Integrating values and consumer involvement. Health research policy and systems / BioMed Central. 2006;4:22. doi:10.1186/1478-4505-4-22 84. Newberry SJ, Ahmadzai N, Motala A, et al. AHRQ Methods for Effective Health Care.Surveillance and identification of signals for updating systematic reviews: Implementation and early experience. Agency for Healthcare Research and Quality (US); 2013. 85. Force USPST. Standards for Guideline Development. 2018. 86. National Institute for Health and Care Excellence. The guidelines manual. 2012.[http://www.nice.org.uk/article/pmg6/resources/non-guidance-the-guidelines-manual-pdf](http://www.nice.org.uk/article/pmg6/resources/non-guidance-the-guidelines-manual-pdf) 87. Martinez Garcia L, McFarlane E, Barnes S, Sanabria AJ, Alonso-Coello P, Alderson P. Updated recommendations: an assessment of NICE clinical guidelines. Implementation science : IS. 2014;9:72. doi:10.1186/1748-5908-9-72 ### Page 189 88. VHA Handbook 1004.07: Financial Relationships between VHA Health Care Professionald and Industry (2014). 89. Raffa SD, Maciejewski ML, Zimmerman LE, et al. A System-Level Approach to Overweight and Obesity in the Veterans Health Administration. J Gen Intern Med. Apr 2017;32(Suppl 1):79-82. doi:10.1007/s11606-016-3948-z 90. Robinson JH, Callister LC, Berry JA, Dearing KA. Patient-centered care and adherence: Definitions and applications to improve outcomes. Journal of the American Academy of Nurse Practitioners. Dec 2008;20(12):600-7. doi:10.1111/j.1745-7599.2008.00360.x 91. Stewart M, Brown JB, Donner A, et al. The impact of patient-centered care on outcomes. J Fam Pract. Sep 2000;49(9):796-804. 92. Vallis M, Piccinini-Vallis H, Sharma AM, Freedhoff Y. Clinical review: modified 5 As: minimal intervention for obesity counseling in primary care. Can Fam Physician. Jan 2013;59(1):27-31. 93. Shared Decision Making Fact Sheet. 2013.[https://www.healthit.gov/sites/default/files/nlc_shared_decision_making_fact_sheet.pdf](https://www.healthit.gov/sites/default/files/nlc_shared_decision_making_fact_sheet.pdf) 94. Institute of Medicine Committee on Quality of Health Care in A. Crossing the Quality Chasm: A New Health System for the 21st Century. National Academies Press (US) Copyright 2001 by the National Academy of Sciences. All rights reserved.; 2001. 95. Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. Proposal for clinical algorithm standards. Medical decision making : an international journal of the Society for Medical Decision Making. Apr-Jun 1992;12(2):149-54. 96. MDApp. Waist to Height Ratio (WHtR) Calculator.[https://www.mdapp.co/waist-to-height-ratio-whtr-calculator-433/](https://www.mdapp.co/waist-to-height-ratio-whtr-calculator-433/) 97. Centers for Disease Control and Prevention. Assessing Your Weight.[http://medbox.iiab.me/modules/en-cdc/www.cdc.gov/healthyweight/assessing/index.html](http://medbox.iiab.me/modules/en-cdc/www.cdc.gov/healthyweight/assessing/index.html) 98. WHO expert consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. Jan 10 2004;363(9403):157-63. doi:10.1016/s0140-6736(03)15268-3 99. Winter JE, MacInnis RJ, Wattanapenpaiboon N, Nowson CA. BMI and all-cause mortality in older adults: a meta-analysis. The American Journal of Clinical Nutrition. 2014;99(4):875-890. doi:10.3945/ajcn.113.068122 100. Sterling R. Fibrosis-4 (FIB-4) Index for Liver Fibrosis.[https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis#creator-insights](https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis#creator-insights) 101. Ratliff JC, Barber JA, Palmese LB, Reutenauer EL, Tek C. Association of prescription H1 antihistamine use with obesity: results from the National Health and Nutrition Examination Survey. Obesity (Silver Spring). Dec 2010;18(12):2398-400. doi:10.1038/oby.2010.176 102. Desalermos A, Russell B, Leggett C, et al. Effect of Obesogenic Medications on Weight- Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). May 2019;27(5):716-723. doi:10.1002/oby.22444 103. Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial.Jama. Nov 10 2004;292(18):2227-36. doi:10.1001/jama.292.18.2227 104. Lopez LM, Ramesh S, Chen M, et al. Progestin-only contraceptives: effects on weight.Cochrane Database Syst Rev. Aug 28 2016;2016(8):Cd008815. doi:10.1002/14651858.CD008815.pub4 105. Gallo MF, Lopez LM, Grimes DA, Schulz KF, Helmerhorst FM. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. Sep 7 2011;(9):Cd003987. doi:10.1002/14651858.CD003987.pub4 106. Lundblad MW, Jacobsen BK, Johansson J, Grimsgaard S, Andersen LF, Hopstock LA. Anthropometric measures are satisfactory substitutes for the DXA-derived visceral adipose ### Page 190 tissue in the association with cardiometabolic risk—The Tromsø Study 2015–2016. Article.Obesity Science and Practice. 2021;7(5):525-534. doi:10.1002/osp4.517 107. Zhu K, Walsh JP, Murray K, Hunter M, Hui J, Hung J. DXA-Derived vs Standard Anthropometric Measures for Predicting Cardiometabolic Risk in Middle-Aged Australian Men and Women. Article. Journal of Clinical Densitometry. 2022;25(3):299-307. doi:10.1016/j.jocd.2022.01.006 108. Potter AW, Looney DP, Tharion WJ, et al. Physical performance and body composition reference values for modern US Marine Corps women. BMJ Nutr Prev Health. 2023;6(2):234-242. doi:10.1136/bmjnph-2023-000757 109. Ode JJ, Pivarnik JM, Reeves MJ, Knous JL. Body mass index as a predictor of percent fat in college athletes and nonathletes. Med Sci Sports Exerc. Mar 2007;39(3):403-9. doi:10.1249/01.mss.0000247008.19127.3e 110. Okorodudu DO, Jumean MF, Montori VM, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta- analysis. Int J Obes (Lond). May 2010;34(5):791-9. doi:10.1038/ijo.2010.5 111. Porto LG, Nogueira RM, Nogueira EC, et al. Agreement between BMI and body fat obesity definitions in a physically active population. Arch Endocrinol Metab. Nov-Dec 2016;60(6):515-525. doi:10.1590/2359-3997000000220 112. Prado CM, Phillips SM, Gonzalez MC, Heymsfield SB. Muscle matters: the effects of medically induced weight loss on skeletal muscle. Lancet Diabetes Endocrinol. Nov 2024;12(11):785-787. doi:10.1016/s2213-8587(24)00272-9 113. Wadden TA, Tsai AG, Tronieri JS. A Protocol to Deliver Intensive Behavioral Therapy (IBT) for Obesity in Primary Care Settings: The MODEL-IBT Program. Obesity (Silver Spring). Oct 2019;27(10):1562-1566. doi:10.1002/oby.22594 114. Wadden TA, Webb VL, Moran CH, Bailer BA. Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation. Mar 6 2012;125(9):1157-70. doi:10.1161/circulationaha.111.039453 115. LeBlanc EL, Patnode CD, Webber EM, Redmond N, Rushkin M, O'Connor EA. Behavioral and Pharmacotherapy Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults: An Updated Systematic Review for the U.S. Preventive Services Task Force. 2018. 116. LeBlanc ES, Patnode CD, Webber EM, Redmond N, Rushkin M, O'Connor EA. Behavioral and Pharmacotherapy Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults: Updated Evidence Report and systematic Review for the U.S. Preventive Services Task Force. JAMA. Sep 18 2018;320(11):1172-1191. doi:10.1001/jama.2018.7777 117. Butryn ML, Webb V, Wadden TA. Behavioral treatment of obesity. The Psychiatric clinics of North America. Dec 2011;34(4):841-59. doi:10.1016/j.psc.2011.08.006 118. Lindstrom J, Peltonen M, Eriksson JG, et al. Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS). Diabetologia. Feb 2013;56(2):284-93. doi:10.1007/s00125-012-2752-5 119. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. May 3 2001;344(18):1343-50. doi:10.1056/nejm200105033441801 120. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. Feb 7 2002;346(6):393- 403. doi:10.1056/NEJMoa012512 121. Leblanc ES, O'Connor E, Whitlock EP, Patnode CD, Kapka T. Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. Oct 4 2011;155(7):434-47. doi:10.7326/0003-4819-155-7-201110040-00006 ### Page 191 122. Miller WR, Rollnick S. Motivational interviewing: Helping people change. 3 ed. Guilford press; 2012. 123. Jeffery RW, Drewnowski A, Epstein LH, et al. Long-term maintenance of weight loss: current status. Health Psychol. Jan 2000;19(1S):5-16. 124. Lutes LD, Damschroder LJ, Masheb R, et al. Behavioral Treatment for Veterans with Obesity: 24-Month Weight Outcomes from the ASPIRE-VA Small Changes Randomized Trial. J Gen Intern Med. Apr 2017;32(Suppl 1):40-47. doi:10.1007/s11606-017-3987-0 125. Harrigan M, Cartmel B, Loftfield E, et al. Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study. J Clin Oncol. Mar 1 2016;34(7):669-76. doi:10.1200/jco.2015.61.6375 126. Christian JG, Byers TE, Christian KK, et al. A computer support program that helps clinicians provide patients with metabolic syndrome tailored counseling to promote weight loss. J Am Diet Assoc. Jan 2011;111(1):75-83. doi:10.1016/j.jada.2010.10.006 127. Demark-Wahnefried W, Jones LW, Snyder DC, et al. Daughters and Mothers Against Breast Cancer (DAMES): main outcomes of a randomized controlled trial of weight loss in overweight mothers with breast cancer and their overweight daughters. Cancer. Aug 15 2014;120(16):2522-34. doi:10.1002/cncr.28761 128. Fischer HH, Fischer IP, Pereira RI, et al. Text Message Support for Weight Loss in Patients With Prediabetes: A Randomized Clinical Trial. Diabetes Care. Aug 2016;39(8):1364-70. doi:10.2337/dc15-2137 129. Godino JG, Merchant G, Norman GJ, et al. Using social and mobile tools for weight loss in overweight and obese young adults (Project SMART): a 2 year, parallel-group, randomised, controlled trial. Lancet Diabetes Endocrinol. Sep 2016;4(9):747-755. doi:10.1016/s2213-8587(16)30105-x 130. Haapala I, Barengo NC, Biggs S, Surakka L, Manninen P. Weight loss by mobile phone: a 1-year effectiveness study. Public Health Nutr. Dec 2009;12(12):2382-91. doi:10.1017/s1368980009005230 131. Little P, Stuart B, Hobbs FR, et al. An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial. Lancet Diabetes Endocrinol. Oct 2016;4(10):821-8. doi:10.1016/s2213- 8587(16)30099-7 132. Morgan PJ, Lubans DR, Collins CE, Warren JM, Callister R. 12-month outcomes and process evaluation of the SHED-IT RCT: an internet-based weight loss program targeting men. Obesity (Silver Spring). Jan 2011;19(1):142-51. doi:10.1038/oby.2010.119 133. Nicklas JM, Zera CA, England LJ, et al. A web-based lifestyle intervention for women with recent gestational diabetes mellitus: a randomized controlled trial. Obstet Gynecol. Sep 2014;124(3):563-70. doi:10.1097/aog.0000000000000420 134. Pacanowski CR, Levitsky DA. Frequent Self-Weighing and Visual Feedback for Weight Loss in Overweight Adults. J Obes. 2015;2015:763680. doi:10.1155/2015/763680 135. Patrick K, Calfas KJ, Norman GJ, et al. Outcomes of a 12-month web-based intervention for overweight and obese men. Ann Behav Med. Dec 2011;42(3):391-401. doi:10.1007/s12160-011-9296-7 136. Shapiro JR, Koro T, Doran N, et al. Text4Diet: a randomized controlled study using text messaging for weight loss behaviors. Prev Med. Nov 2012;55(5):412-7. doi:10.1016/j.ypmed.2012.08.011 137. Thomas JG, Raynor HA, Bond DS, et al. Weight loss in Weight Watchers Online with and without an activity tracking device compared to control: A randomized trial. Obesity (Silver Spring). Jun 2017;25(6):1014-1021. doi:10.1002/oby.21846 138. Mai K, Brachs M, Leupelt V, et al. Effects of a combined dietary, exercise and behavioral intervention and sympathetic system on body weight maintenance after intended weight ### Page 192 loss: Results of a randomized controlled trial. Metabolism. Jun 2018;83:60-67. doi:10.1016/j.metabol.2018.01.003 139. Das SK, Bukhari AS, Taetzsch AG, et al. Randomized trial of a novel lifestyle intervention compared with the Diabetes Prevention Program for weight loss in adult dependents of military service members. Article. American Journal of Clinical Nutrition. 2021;114(4):1546-1559. doi:10.1093/ajcn/nqab259 140. Washburn RA, Szabo-Reed AN, Gorczyca AM, et al. A Randomized Trial Evaluating Exercise for the Prevention of Weight Regain. Article. Obesity. 2021;29(1):62-70. doi:10.1002/oby.23022 141. Duncan MJ, Fenton S, Brown WJ, et al. Efficacy of a multi-component m-health weight- loss intervention in overweight and obese adults: A randomised controlled trial. Article.International Journal of Environmental Research and Public Health. 2020;17(17):1-21. doi:10.3390/ijerph17176200 142. Astbury NM, Piernas C, Hartmann-Boyce J, Lapworth S, Aveyard P, Jebb SA. A systematic review and meta-analysis of the effectiveness of meal replacements for weight loss. Obes Rev. Apr 2019;20(4):569-587. doi:10.1111/obr.12816 143. Bazzano LA, Hu T, Reynolds K, et al. Effects of low-carbohydrate and low-fat diets: a randomized trial. Ann Intern Med. Sep 2 2014;161(5):309-18. doi:10.7326/m14-0180 144. Brinkworth GD, Wycherley TP, Noakes M, Buckley JD, Clifton PM. Long-term effects of a very-low-carbohydrate weight-loss diet and an isocaloric low-fat diet on bone health in obese adults. Nutrition. Sep 2016;32(9):1033-6. doi:10.1016/j.nut.2016.03.003 145. Catenacci VA, Pan Z, Ostendorf D, et al. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity (Silver Spring). Sep 2016;24(9):1874-83. doi:10.1002/oby.21581 146. Headland ML, Clifton PM, Keogh JB. Effect of intermittent compared to continuous energy restriction on weight loss and weight maintenance after 12 months in healthy overweight or obese adults. Int J Obes (Lond). Nov 23 2018;doi:10.1038/s41366-018-0247-2 147. Johnston BC, Kanters S, Bandayrel K, et al. Comparison of weight loss among named diet programs in overweight and obese adults: a meta-analysis. JAMA. Sep 3 2014;312(9):923-33. doi:10.1001/jama.2014.10397 148. Moreno B, Bellido D, Sajoux I, et al. Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. Endocrine. Dec 2014;47(3):793-805. doi:10.1007/s12020-014-0192-3 149. Sackner-Bernstein J, Kanter D, Kaul S. Dietary Intervention for Overweight and Obese Adults: Comparison of Low-Carbohydrate and Low-Fat Diets. A Meta-Analysis. PLoS One. 2015;10(10):e0139817. doi:10.1371/journal.pone.0139817 150. Roman YM, Dominguez MC, Easow TM, Pasupuleti V, White CM, Hernandez AV. Effects of intermittent versus continuous dieting on weight and body composition in obese and overweight people: a systematic review and meta-analysis of randomized controlled trials.Int J Obes (Lond). Sep 11 2018;doi:10.1038/s41366-018-0204-0 151. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: Secondary analysis of a randomized controlled trial. Clin Nutr. Dec 2018;37(6 Pt A):1871- 1878. doi:10.1016/j.clnu.2017.11.018 152. Sundfor TM, Svendsen M, Tonstad S. Effect of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk: A randomized 1-year trial. Nutr Metab Cardiovasc Dis. Jul 2018;28(7):698-706. doi:10.1016/j.numecd.2018.03.009 153. Zinn C, McPhee J, Harris N, Williden M, Prendergast K, Schofield G. A 12-week low- carbohydrate, high-fat diet improves metabolic health outcomes over a control diet in a ### Page 193 randomised controlled trial with overweight defence force personnel. Appl Physiol Nutr Metab. Nov 2017;42(11):1158-1164. doi:10.1139/apnm-2017-0260 154. Khalafi M, Maleki AH, Ehsanifar M, Symonds ME, Rosenkranz SK. Longer-term effects of intermittent fasting on body composition and cardiometabolic health in adults with overweight and obesity: A systematic review and meta-analysis. Article in Press. Obesity Reviews. 2024;doi:10.1111/obr.13855 155. Kim KK, Kang JH, Kim EM. Updated Meta-Analysis of Studies from 2011 to 2021 Comparing the Effectiveness of Intermittent Energy Restriction and Continuous Energy Restriction. Article. Journal of Obesity and Metabolic Syndrome. 2022;31(3):230-244. doi:10.7570/jomes22050 156. Ge L, Sadeghirad B, Ball GDC, et al. Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: Systematic review and network meta-analysis of randomised trials. Review. The BMJ. 2020;369doi:10.1136/bmj.m696 157. Chawla S, Silva FT, Medeiros SA, Mekary RA, Radenkovic D. The effect of low-fat and low-carbohydrate diets on weight loss and lipid levels: A systematic review and meta- analysis. Review. Nutrients. 2020;12(12):1-21. doi:10.3390/nu12123774 158. Choi YJ, Jeon SM, Shin S. Impact of a ketogenic diet on metabolic parameters in patients with obesity or overweight and with or without type 2 diabetes: A meta-analysis of randomized controlled trials. Article. Nutrients. 2020;12(7):1-19. doi:10.3390/nu12072005 159. Fatahi S, Fotros D, Sohouli MH, Vahidshahi K, Rohani P, Guimarães NS. Meal replacements on obesity and leptin: a systematic review and meta-analysis. Article in Press. Reviews in Endocrine and Metabolic Disorders. 2024;doi:10.1007/s11154-024- 09918-5 160. Chekima K, Yan SW, Lee SWH, et al. Low glycaemic index or low glycaemic load diets for people with overweight or obesity. Article. Cochrane Database of Systematic Reviews. 2023;2023(6)doi:10.1002/14651858.CD005105.pub3 161. Melgar B, Diaz-Arocutipa C, Huerta-Rengifo C, Piscoya A, Barboza JJ, Hernandez AV. Vegetarian diets on anthropometric, metabolic and blood pressure outcomes in people with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Review. International Journal of Obesity. 2023;47(10):903-910. doi:10.1038/s41366-023-01357-7 162. Turner-Mcgrievy GM, Wilcox S, Frongillo EA, et al. Effect of a Plant-Based vs Omnivorous Soul Food Diet on Weight and Lipid Levels among African American Adults: A Randomized Clinical Trial. Article. JAMA Network Open. 2023;6(1):E2250626. doi:10.1001/jamanetworkopen.2022.50626 163. Seimon RV, Wild-Taylor AL, Keating SE, et al. Effect of weight loss via severe vs moderate energy restriction on lean mass and body composition among postmenopausal women with obesity: The tempo diet randomized clinical trial. Article. JAMA Network Open. 2019;2(10)doi:10.1001/jamanetworkopen.2019.13733 164. Cho E, Kim S, Kim HJ, et al. Effectiveness of a protein-supplemented very-low-calorie diet program for weight loss: a randomized controlled trial in South Korea. Front Nutr. 2024;11:1370737. doi:10.3389/fnut.2024.1370737 165. Lutze J, Taylor P, Brinkworth GD, et al. Psychological well-being response to high protein and high carbohydrate weight loss diets in overweight and obese men: A randomised trial.e-SPEN Journal. 2013;8(6):e235-e240. 166. Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr. Mar 2013;97(3):505- 16. doi:10.3945/ajcn.112.042457 167. Bravata DM, Sanders L, Huang J, et al. Efficacy and safety of low-carbohydrate diets: a systematic review. JAMA. Apr 9 2003;289(14):1837-50. doi:10.1001/jama.289.14.1837 ### Page 194 168. Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. May 22 2003;348(21):2082-90. doi:10.1056/NEJMoa022207 169. Hu T, Mills KT, Yao L, et al. Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol. Oct 1 2012;176 Suppl 7:S44-54. doi:10.1093/aje/kws264 170. Nordmann AJ, Nordmann A, Briel M, et al. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Archives of internal medicine. Feb 13 2006;166(3):285-93. doi:10.1001/archinte.166.3.285 171. Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. Feb 26 2009;360(9):859- 73. doi:10.1056/NEJMoa0804748 172. Samaha FF, Iqbal N, Seshadri P, et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. May 22 2003;348(21):2074-81. doi:10.1056/NEJMoa022637 173. Wycherley TP, Buckley JD, Noakes M, Clifton PM, Brinkworth GD. Comparison of the effects of weight loss from a high-protein versus standard-protein energy-restricted diet on strength and aerobic capacity in overweight and obese men. Eur J Nutr. Feb 2013;52(1):317-25. doi:10.1007/s00394-012-0338-0 174. Yancy WS, Jr., Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. May 18 2004;140(10):769-77. doi:10.7326/0003-4819- 140-10-200405180-00006 175. Klempel MC, Kroeger CM, Norkeviciute E, Goslawski M, Phillips SA, Varady KA. Benefit of a low-fat over high-fat diet on vascular health during alternate day fasting. Nutr Diabetes. May 27 2013;3:e71. doi:10.1038/nutd.2013.14 176. Soltani S, Shirani F, Chitsazi MJ, Salehi-Abargouei A. The effect of dietary approaches to stop hypertension (DASH) diet on weight and body composition in adults: a systematic review and meta-analysis of randomized controlled clinical trials. Obes Rev. May 2016;17(5):442-54. doi:10.1111/obr.12391 177. Parretti HM, Jebb SA, Johns DJ, Lewis AL, Christian-Brown AM, Aveyard P. Clinical effectiveness of very-low-energy diets in the management of weight loss: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. Mar 2016;17(3):225- 34. doi:10.1111/obr.12366 178. Deemer SE, Plaisance EP, Martins C. Impact of ketosis on appetite regulation-a review.Nutr Res. May 2020;77:1-11. doi:10.1016/j.nutres.2020.02.010 179. Martins C, Nymo S, Truby H, Rehfeld JF, Hunter GR, Gower BA. Association Between Ketosis and Changes in Appetite Markers with Weight Loss Following a Very Low-Energy Diet. Obesity (Silver Spring). Dec 2020;28(12):2331-2338. doi:10.1002/oby.23011 180. Roekenes J, Martins C. Ketogenic diets and appetite regulation. Curr Opin Clin Nutr Metab Care. Jul 1 2021;24(4):359-363. doi:10.1097/mco.0000000000000760 181. Gibson AA, Seimon RV, Lee CM, et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev. Jan 2015;16(1):64-76. doi:10.1111/obr.12230 182. Stanek A, Brożyna-Tkaczyk K, Zolghadri S, Cholewka A, Myśliński W. The Role ofIntermittent Energy Restriction Diet on Metabolic Profile and Weight Loss among Obese Adults. Nutrients. Apr 5 2022;14(7)doi:10.3390/nu14071509 183. Varady KA, Cienfuegos S, Ezpeleta M, Gabel K. Cardiometabolic Benefits of Intermittent Fasting. Annu Rev Nutr. Oct 11 2021;41:333-361. doi:10.1146/annurev-nutr-052020- 041327 ### Page 195 184. Anton SD, Moehl K, Donahoo WT, et al. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). Feb 2018;26(2):254-268. doi:10.1002/oby.22065 185. Noakes M, Foster PR, Keogh JB, Clifton PM. Meal replacements are as effective as structured weight-loss diets for treating obesity in adults with features of metabolic syndrome. J Nutr. Aug 2004;134(8):1894-9. doi:10.1093/jn/134.8.1894 186. Chen C, Zhang D, Ye M, You Y, Song Y, Chen X. Effects of various exercise types on inflammatory response in individuals with overweight and obesity: a systematic review and network meta-analysis of randomized controlled trials. Article in Press. International Journal of Obesity. 2024;doi:10.1038/s41366-024-01649-6 187. Hu C, Sun D, Fang Y, et al. Mixed comparison of different exercise interventions on physical functioning in adult patients with morbid obesity following bariatric surgery: a systematic review and network meta-analysis. Review. Frontiers in Endocrinology. 2024;15doi:10.3389/fendo.2024.1465718 188. Guo Z, Li M, Cai J, Gong W, Liu Y, Liu Z. Effect of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Fat Loss and Cardiorespiratory Fitness in the Young and Middle-Aged a Systematic Review and Meta-Analysis. Review. International Journal of Environmental Research and Public Health. 2023;20(6)doi:10.3390/ijerph20064741 189. Hao Z, Liu K, Qi W, Zhang X, Zhou L, Chen P. Which exercise interventions are more helpful in treating primary obesity in young adults? A systematic review and Bayesian network meta-analysis. Article. Archives of Medical Science. 2023;19(4):865-883. doi:10.5114/aoms/153479 190. Batrakoulis A, Jamurtas AZ, Metsios GS, et al. Comparative Efficacy of 5 Exercise Types on Cardiometabolic Health in Overweight and Obese Adults: A Systematic Review and Network Meta-Analysis of 81 Randomized Controlled Trials. Article. Circulation: Cardiovascular Quality and Outcomes. 2022;15(6):E008243. doi:10.1161/CIRCOUTCOMES.121.008243 191. Poon ETC, Li HY, Little JP, Wong SHS, Ho RST. Efficacy of Interval Training in Improving Body Composition and Adiposity in Apparently Healthy Adults: An Umbrella Review with Meta-Analysis. Article. Sports medicine (Auckland, NZ). 2024;54(11):2817-2840. doi:10.1007/s40279-024-02070-9 192. van Baak MA, Pramono A, Battista F, et al. Effect of different types of regular exercise on physical fitness in adults with overweight or obesity: Systematic review and meta- analyses. Article. Obesity Reviews. 2021;22(S4)doi:10.1111/obr.13239 193. Alizaei Yousefabadi H, Niyazi A, Alaee S, Fathi M, Mohammad Rahimi GR. Anti- Inflammatory Effects of Exercise on Metabolic Syndrome Patients: A Systematic Review and Meta-Analysis. Article. Biological research for nursing. 2021;23(2):280-292. doi:10.1177/1099800420958068 194. Carraça EV, Encantado J, Battista F, et al. Effect of exercise training on psychological outcomes in adults with overweight or obesity: A systematic review and meta-analysis. Article. Obesity Reviews. 2021;22(S4)doi:10.1111/obr.13261 195. Chavarrias M, Villafaina S, Lavín-Pérez AM, Carlos-Vivas J, Merellano-Navarro E, Pérez- Gómez J. Zumba®, fat mass and maximum oxygen consumption: A systematic review and meta-analysis. Review. International Journal of Environmental Research and Public Health. 2021;18(1):1-13. doi:10.3390/ijerph18010105 196. de Souza F, Lanzendorf FN, de Souza MMM, Schuelter-Trevisol F, Trevisol DJ. Effectiveness of martial arts exercise on anthropometric and body composition parameters of overweight and obese subjects: a systematic review and meta-analysis. Article. BMC public health. 2020;20(1):1246. doi:10.1186/s12889-020-09340-x ### Page 196 197. Letnes JM, Berglund I, Johnson KE, et al. Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: The Generation 100 randomized trial. Article.European Heart Journal. 2022;43(21):2065-2075. doi:10.1093/eurheartj/ehab721 198. Cheng CC, Hsu CY, Liu JF. Effects of dietary and exercise intervention on weight loss and body composition in obese postmenopausal women: a systematic review and meta- analysis. Menopause. Jul 2018;25(7):772-782. doi:10.1097/gme.0000000000001085 199. Schwingshackl L, Dias S, Hoffmann G. Impact of long-term lifestyle programmes on weight loss and cardiovascular risk factors in overweight/obese participants: a systematic review and network meta-analysis. Syst Rev. Oct 30 2014;3:130. doi:10.1186/2046-4053- 3-130 200. Creasy SA, Rogers RJ, Davis KK, Gibbs BB, Kershaw EE, Jakicic JM. Effects of supervised and unsupervised physical activity programmes for weight loss. Obes Sci Pract. Jun 2017;3(2):143-152. doi:10.1002/osp4.107 201. Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK. American College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. Feb 2009;41(2):459-71. doi:10.1249/MSS.0b013e3181949333 202. Slentz CA, Duscha BD, Johnson JL, et al. Effects of the amount of exercise on body weight, body composition, and measures of central obesity: STRRIDE--a randomized controlled study. Archives of internal medicine. Jan 12 2004;164(1):31-9. doi:10.1001/archinte.164.1.31 203. Miller WC, Koceja DM, Hamilton EJ. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Int J Obes Relat Metab Disord. Oct 1997;21(10):941-7. doi:10.1038/sj.ijo.0800499 204. Dutheil F, Lac G, Lesourd B, et al. Different modalities of exercise to reduce visceral fat mass and cardiovascular risk in metabolic syndrome: the RESOLVE randomized trial. Int J Cardiol. Oct 9 2013;168(4):3634-42. doi:10.1016/j.ijcard.2013.05.012 205. Fanning J, Walkup MP, Ambrosius WT, et al. Change in health-related quality of life and social cognitive outcomes in obese, older adults in a randomized controlled weight loss trial: Does physical activity behavior matter? J Behav Med. Jun 2018;41(3):299-308. doi:10.1007/s10865-017-9903-6 206. Qiu H, Zheng W, Zhou X, Liu Q, Zhao X. Training modalities for elder sarcopenic obesity: a systematic review and network meta-analysis. Front Nutr. 2025;12:1537291. doi:10.3389/fnut.2025.1537291 207. Pontzer H, Durazo-Arvizu R, Dugas LR, et al. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans. Curr Biol. Feb 8 2016;26(3):410-7. doi:10.1016/j.cub.2015.12.046 208. Martin CK, Johnson WD, Myers CA, et al. Effect of different doses of supervised exercise on food intake, metabolism, and non-exercise physical activity: The E-MECHANIC randomized controlled trial. Am J Clin Nutr. Sep 1 2019;110(3):583-592. doi:10.1093/ajcn/nqz054 209. Broskey NT, Martin CK, Burton JH, Church TS, Ravussin E, Redman LM. Effect of Aerobic Exercise-induced Weight Loss on the Components of Daily Energy Expenditure.Med Sci Sports Exerc. Oct 1 2021;53(10):2164-2172. doi:10.1249/mss.0000000000002689 210. American College of Sports Medicine. Physical Activity Guidelines.[https://acsm.org/education-resources/trending-topics-resources/physical-activity-guidelines/](https://acsm.org/education-resources/trending-topics-resources/physical-activity-guidelines/) 211. Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans.JAMA. Nov 20 2018;320(19):2020-2028. doi:10.1001/jama.2018.14854 ### Page 197 212. Services USDoHaH. Physical Activity Guidelines for Americans. U.S. Department of Health and Human Services. Accessed October 7, 2019,[https://health.gov/paguidelines/second-edition/pdf/Physical_Activity_Guidelines_2nd_edition.pdf](https://health.gov/paguidelines/second-edition/pdf/Physical_Activity_Guidelines_2nd_edition.pdf) 213. Puhl RM. Weight Stigma and Barriers to Effective Obesity Care. Gastroenterol Clin North Am. Jun 2023;52(2):417-428. doi:10.1016/j.gtc.2023.02.002 214. Chew HSJ, Chng S, Rajasegaran NN, Choy KH, Chong YY. Effectiveness of acceptance and commitment therapy on weight, eating behaviours and psychological outcomes: a systematic review and meta-analysis. Review. Eating and Weight Disorders. 2023;28(1)doi:10.1007/s40519-023-01535-6 215. Pearl RL, Wadden TA, Bach C, Tronieri JS, Berkowitz RI. Six-Month Follow-up from a Randomized Controlled Trial of the Weight BIAS Program. Article. Obesity. 2020;28(10):1878-1888. doi:10.1002/oby.22931 216. Pearl RL, Wadden TA, Bach C, et al. Long-Term Effects of an Internalized Weight Stigma Intervention: A Randomized Controlled Trial. Article. Journal of Consulting and Clinical Psychology. 2023;91(7):398-410. doi:10.1037/ccp0000819 217. Braun TD, Olson K, Panza E, et al. Internalized weight stigma in women with class III obesity: A randomized controlled trial of a virtual lifestyle modification intervention followed by a mindful self-compassion intervention. Article. Obesity Science and Practice. 2022;8(6):816-827. doi:10.1002/osp4.616 218. Palmeira L, Pinto-Gouveia J, Cunha M. Exploring the efficacy of an acceptance, mindfulness & compassionate-based group intervention for women struggling with their weight (Kg-Free): A randomized controlled trial. Appetite. May 1 2017;112:107-116. doi:10.1016/j.appet.2017.01.027 219. Levin ME, Petersen JM, Durward C, et al. A randomized controlled trial of online acceptance and commitment therapy to improve diet and physical activity among adults who are overweight/obese. Transl Behav Med. Jun 17 2021;11(6):1216-1225. doi:10.1093/tbm/ibaa123 220. Berman MI, Park J, Kragenbrink ME, Hegel MT. Accept Yourself! A Pilot Randomized Controlled Trial of a Self-Acceptance-Based Treatment for Large-Bodied Women With Depression. Behav Ther. Sep 2022;53(5):913-926. doi:10.1016/j.beth.2022.03.002 221. Potts S, Krafft J, Levin ME. A Pilot Randomized Controlled Trial of Acceptance and Commitment Therapy Guided Self-Help for Overweight and Obese Adults High in Weight Self-Stigma. Behav Modif. Jan 2022;46(1):178-201. doi:10.1177/0145445520975112 222. Boston Scientific Corporation. Orbera™ Intragastric Balloon System.[https://www.bostonscientific.com/en-US/products/endoluminal-surgery-devices/orbera-intragastric-balloon-system.html](https://www.bostonscientific.com/en-US/products/endoluminal-surgery-devices/orbera-intragastric-balloon-system.html) 223. Spatz FGIA Inc. Spatz3 Adjustable Gastric Balloon.[https://www.spatzmedical.com/](https://www.spatzmedical.com/) 224. Maggard-Gibbons M SP, Girgis MD, et al. . Endoscopic Bariatric Interventions versus Lifestyle Interventions or Surgery for Weight Loss in Patients with Obesity: A Systematic Review and Meta-analysis. 2022; 225. Shah R, Davitkov P, Abu Dayyeh BK, Saumoy M, Murad MH. AGA Technical Review on Intragastric Balloons in the Management of Obesity. Article. Gastroenterology. 2021;160(5):1811-1830. doi:10.1053/j.gastro.2021.02.043 226. Brooks J, Srivastava ED, Mathus-Vliegen EM. One-year adjustable intragastric balloons: results in 73 consecutive patients in the U.K. Obes Surg. May 2014;24(5):813-9. doi:10.1007/s11695-014-1176-3 227. Wiggins T, Sharma O, Sarfaraz Y, Fry H, Baker J, Singhal R. Safety and Efficacy of 12- Month Intra-gastric Balloon-Series of over 1100 Patients. Obes Surg. Jan 2024;34(1):176- 182. doi:10.1007/s11695-023-06953-0 ### Page 198 228. Department of Defense. Policy on Bariatric Surgical Procedures for Active Duty Service Members.[https://health.mil/reference-center/policies/2007/05/11/policy-on-bariatric-surgical-procedures-for-active-duty-service-members](https://health.mil/reference-center/policies/2007/05/11/policy-on-bariatric-surgical-procedures-for-active-duty-service-members) 229. Department of Defense. DOD INSTRUCTION 6130.03, VOLUME 2 MEDICAL STANDARDS FOR MILITARY SERVICE: RETENTION.[https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/613003_vol02.PDF?ver=vx1spUpNVLcc-0-rov00Sg%3d%3d](https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/613003_vol02.PDF?ver=vx1spUpNVLcc-0-rov00Sg%3d%3d) 230. Department of Defense. DOD INSTRUCTION 6130.03, VOLUME 1 MEDICAL STANDARDS FOR MILITARY SERVICE: APPOINTMENT, ENLISTMENT, OR INDUCTION.[https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/613003_vol01.pdf?ver=B0uhh9e1k_MDTz4PuNU8Aw%3d%3d](https://www.esd.whs.mil/Portals/54/Documents/DD/issuances/dodi/613003_vol01.pdf?ver=B0uhh9e1k_MDTz4PuNU8Aw%3d%3d) 231. Choy K, Abbitt D, Kovar A, et al. Weighing your options-intragastric balloon versus semaglutide. Surgical endoscopy. Oct 2024;38(10):6070-6075. doi:10.1007/s00464-024- 11169-z 232. Abbitt D, Choy K, Kovar A, Jones TS, Wikiel KJ, Jones EL. Weight regain after intragastric balloon for pre-surgical weight loss. World J Gastrointest Surg. Jul 27 2024;16(7):2040- 2046. doi:10.4240/wjgs.v16.i7.2040 233. Maghrabi AH, Wolski K, Abood B, et al. Two-year outcomes on bone density and fracture incidence in patients with T2DM randomized to bariatric surgery versus intensive medical therapy. Obesity (Silver Spring). Dec 2015;23(12):2344-8. doi:10.1002/oby.21150 234. Laurenius A. How can we treat postbariatric hypoglycemia by medical nutrition therapy?Surg Obes Relat Dis. May 2017;13(5):896-898. doi:10.1016/j.soard.2017.02.011 235. Eisenberg D, Azagury DE, Ghiassi S, Grover BT, Kim JJ. ASMBS Position Statement on Postprandial Hyperinsulinemic Hypoglycemia after Bariatric Surgery. Surg Obes Relat Dis. Mar 2017;13(3):371-378. doi:10.1016/j.soard.2016.12.005 236. De Luca M, Zese M, Silverii GA, et al. Bariatric Surgery for Patients with Overweight/Obesity. A Comprehensive Grading Methodology and Network Metanalysis of Randomized Controlled Trials on Weight Loss Outcomes and Adverse Events. Review.Obesity Surgery. 2023;33(12):4147-4158. doi:10.1007/s11695-023-06909-4 237. Małczak P, Mizera M, Lee Y, et al. Quality of Life After Bariatric Surgery—a Systematic Review with Bayesian Network Meta-analysis. Article. Obesity Surgery. 2021;31(12):5213- 5223. doi:10.1007/s11695-021-05687-1 238. Ablett AD, Boyle BR, Avenell A. Fractures in Adults After Weight Loss from Bariatric Surgery and Weight Management Programs for Obesity: Systematic Review and Meta- analysis. Article. Obesity surgery. 2019;29(4):1327-1342. doi:10.1007/s11695-018-03685- 4 239. Cummings DE, Arterburn DE, Westbrook EO, et al. Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: the CROSSROADS randomised controlled trial. Diabetologia. May 2016;59(5):945-53. doi:10.1007/s00125-016-3903-x 240. Xiang AH, Trigo E, Martinez M, et al. Impact of Gastric Banding Versus Metformin on β- Cell Function in Adults With Impaired Glucose Tolerance or Mild Type 2 Diabetes.Diabetes Care. Dec 2018;41(12):2544-2551. doi:10.2337/dc18-1662 241. Simonson DC, Halperin F, Foster K, Vernon A, Goldfine AB. Clinical and Patient-Centered Outcomes in Obese Patients With Type 2 Diabetes 3 Years After Randomization to Roux- en-Y Gastric Bypass Surgery Versus Intensive Lifestyle Management: The SLIMM-T2D Study. Diabetes Care. Apr 2018;41(4):670-679. doi:10.2337/dc17-0487 242. Courcoulas AP, Gallagher JW, Neiberg RH, et al. Bariatric Surgery vs Lifestyle Intervention for Diabetes Treatment: 5-Year Outcomes From a Randomized Trial. J Clin Endocrinol Metab. Mar 1 2020;105(3):866-76. doi:10.1210/clinem/dgaa006 ### Page 199 243. Ikramuddin S, Korner J, Lee WJ, et al. Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood Pressure at 5 Years in the Diabetes Surgery Study. Jama. Jan 16 2018;319(3):266-278. doi:10.1001/jama.2017.20813 244. Schauer PR, Bhatt DL, Kirwan JP, et al. Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. N Engl J Med. Feb 16 2017;376(7):641-651. doi:10.1056/NEJMoa1600869 245. Axelrod CL, Hari A, Dantas WS, Kashyap SR, Schauer PR, Kirwan JP. Metabolomic Fingerprints of Medical Therapy Versus Bariatric Surgery in Patients With Obesity and Type 2 Diabetes: The STAMPEDE Trial. Diabetes Care. Nov 1 2024;47(11):2024-2032. doi:10.2337/dc24-0859 246. Cohen RV, Pereira TV, Aboud CM, et al. Effect of Gastric Bypass vs Best Medical Treatment on Early-Stage Chronic Kidney Disease in Patients With Type 2 Diabetes and Obesity: A Randomized Clinical Trial. JAMA Surg. Aug 1 2020;155(8):e200420. doi:10.1001/jamasurg.2020.0420 247. Cheng A, Yeoh E, Moh A, et al. Roux-en-Y gastric bypass versus best medical treatment for type 2 diabetes mellitus in adults with body mass index between 27 and 32 kg/m(2): A 5-year randomized controlled trial. Diabetes Res Clin Pract. Jun 2022;188:109900. doi:10.1016/j.diabres.2022.109900 248. Liang Z, Wu Q, Chen B, Yu P, Zhao H, Ouyang X. Effect of laparoscopic Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus with hypertension: a randomized controlled trial. Diabetes Res Clin Pract. Jul 2013;101(1):50-6. doi:10.1016/j.diabres.2013.04.005 249. Feigel-Guiller B, Drui D, Dimet J, et al. Laparoscopic Gastric Banding in Obese Patients with Sleep Apnea: A 3-Year Controlled Study and Follow-up After 10 Years. Obes Surg. Oct 2015;25(10):1886-92. doi:10.1007/s11695-015-1627-5 250. Dixon JB, Schachter LM, O'Brien PE, et al. Surgical vs conventional therapy for weight loss treatment of obstructive sleep apnea: a randomized controlled trial. Jama. Sep 19 2012;308(11):1142-9. doi:10.1001/2012.jama.11580 251. Dowsey MM, Brown WA, Cochrane A, Burton PR, Liew D, Choong PF. Effect of Bariatric Surgery on Risk of Complications After Total Knee Arthroplasty: A Randomized Clinical Trial. JAMA Netw Open. Apr 1 2022;5(4):e226722. doi:10.1001/jamanetworkopen.2022.6722 252. Spaggiari M, Di Cocco P, Tulla K, et al. Simultaneous robotic kidney transplantation and bariatric surgery for morbidly obese patients with end-stage renal failure. Am J Transplant. Apr 2021;21(4):1525-1534. doi:10.1111/ajt.16322 253. O'Brien PE, Brennan L, Laurie C, Brown W. Intensive medical weight loss or laparoscopic adjustable gastric banding in the treatment of mild to moderate obesity: long-term follow- up of a prospective randomised trial. Obes Surg. Sep 2013;23(9):1345-53. doi:10.1007/s11695-013-0990-3 254. Mollan SP, Mitchell JL, Ottridge RS, et al. Effectiveness of Bariatric Surgery vs Community Weight Management Intervention for the Treatment of Idiopathic Intracranial Hypertension: A Randomized Clinical Trial. JAMA Neurol. Jun 1 2021;78(6):678-686. doi:10.1001/jamaneurol.2021.0659 255. Maciejewski ML, Arterburn DE, Van Scoyoc L, et al. Bariatric Surgery and Long-term Durability of Weight Loss. JAMA Surg. Nov 1 2016;151(11):1046-1055. doi:10.1001/jamasurg.2016.2317 256. Clapp B, Abi Mosleh K, Glasgow AE, et al. Bariatric surgery is as safe as other common operations: an analysis of the ACS-NSQIP. Surg Obes Relat Dis. Jun 2024;20(6):515-525. doi:10.1016/j.soard.2023.11.017 ### Page 200 257. Garcia FK, Mulder BC, Hazebroek EJ, Koelen MA, Veen EJ, Verkooijen KT. Bariatric surgery stigma from the perspective of patients: A scoping review. J Adv Nurs. Jun 2024;80(6):2252-2272. doi:10.1111/jan.15994 258. Funk LM, Jolles SA, Greenberg CC, et al. Primary care physician decision making regarding severe obesity treatment and bariatric surgery: a qualitative study. Surg Obes Relat Dis. May 2016;12(4):893-901. doi:10.1016/j.soard.2015.11.028 259. Smith VA, Zepel L, Kawatkar AA, et al. Health Expenditures After Bariatric Surgery: A Retrospective Cohort Study. Ann Surg. Dec 1 2024;280(6):e8-e16. doi:10.1097/sla.0000000000006333 260. Eisenberg D, Shikora SA, Aarts E, et al. 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) Indications for Metabolic and Bariatric Surgery. Obes Surg. Jan 2023;33(1):3-14. doi:10.1007/s11695-022-06332-1 261. Boston Scientific Corporation. OverStitch™ NXT Endoscopic Suturing System.[https://www.bostonscientific.com/content/dam/bostonscientific/endo/portfolio-group/endoscopic-closure/overstitch-nxt-dfu.pdf](https://www.bostonscientific.com/content/dam/bostonscientific/endo/portfolio-group/endoscopic-closure/overstitch-nxt-dfu.pdf) 262. Huberty V, Boskoski I, Bove V, et al. Endoscopic sutured gastroplasty in addition to lifestyle modification: Short-term efficacy in a controlled randomised trial. Article. Gut. 2021;70(8):1479-1485. doi:10.1136/gutjnl-2020-322026 263. Abu Dayyeh BK, Bazerbachi F, Vargas EJ, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Article. The Lancet. 2022;400(10350):441-451. doi:10.1016/S0140-6736(22)01280-6 264. de Miranda Neto AA, de Moura DTH, Ribeiro IB, et al. Efficacy and Safety of Endoscopic Sleeve Gastroplasty at Mid Term in the Management of Overweight and Obese Patients: a Systematic Review and Meta-Analysis. Obes Surg. May 2020;30(5):1971-1987. doi:10.1007/s11695-020-04449-9 265. Hedjoudje A, Abu Dayyeh BK, Cheskin LJ, et al. Efficacy and Safety of Endoscopic Sleeve Gastroplasty: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. May 2020;18(5):1043-1053.e4. doi:10.1016/j.cgh.2019.08.022 266. Mohan BP, Asokkumar R, Khan SR, et al. Outcomes of endoscopic sleeve gastroplasty; how does it compare to laparoscopic sleeve gastrectomy? A systematic review and meta- analysis. Endosc Int Open. Apr 2020;8(4):E558-e565. doi:10.1055/a-1120-8350 267. Yoon JY, Arau RT. The Efficacy and Safety of Endoscopic Sleeve Gastroplasty as an Alternative to Laparoscopic Sleeve Gastrectomy. Clin Endosc. Jan 2021;54(1):17-24. doi:10.5946/ce.2021.019 268. Haseeb M, Chhatwal J, Xiao J, Jirapinyo P, Thompson CC. Semaglutide vs Endoscopic Sleeve Gastroplasty for Weight Loss. JAMA Netw Open. Apr 1 2024;7(4):e246221. doi:10.1001/jamanetworkopen.2024.6221 269. Grunvald E, Shah R, Hernaez R, et al. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. Nov 2022;163(5):1198-1225. doi:10.1053/j.gastro.2022.08.045 270. Wadden TA, Tronieri JS, Butryn ML. Lifestyle modification approaches for the treatment of obesity in adults. Am Psychol. Feb-Mar 2020;75(2):235-251. doi:10.1037/amp0000517 271. Wadden TA, West DS, Neiberg RH, et al. One-year weight losses in the Look AHEAD study: factors associated with success. Obesity (Silver Spring). Apr 2009;17(4):713-22. doi:10.1038/oby.2008.637 272. Christian JG, Tsai AG, Bessesen DH. Interpreting weight losses from lifestyle modification trials: using categorical data. Int J Obes (Lond). Jan 2010;34(1):207-9. doi:10.1038/ijo.2009.213 ### Page 201 273. Unick JL, Hogan PE, Neiberg RH, et al. Evaluation of early weight loss thresholds for identifying nonresponders to an intensive lifestyle intervention. Obesity (Silver Spring). Jul 2014;22(7):1608-16. doi:10.1002/oby.20777 274. Executive summary: Guidelines (2013) for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society published by the Obesity Society and American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Based on a systematic review from the The Obesity Expert Panel, 2013.Obesity (Silver Spring). Jul 2014;22 Suppl 2:S5-39. doi:10.1002/oby.20821 275. Golovaty I, Hagan S. Lifestyle Intervention Requirements for Novel Antiobesity Medications-Necessary Adjunct or Harmful Gatekeeper? JAMA Intern Med. Mar 1 2025;185(3):255-256. doi:10.1001/jamainternmed.2024.6450 276. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. Article. New England Journal of Medicine. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183 277. Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. Jama. Apr 13 2021;325(14):1403- 1413. doi:10.1001/jama.2021.1831 278. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. Jul 21 2022;387(3):205-216. doi:10.1056/NEJMoa2206038 279. Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity: The SURMOUNT-4 Randomized Clinical Trial. Article. JAMA. 2024;331(1):38-48. doi:10.1001/jama.2023.24945 280. Wadden TA, Chao AM, Moore M, et al. The Role of Lifestyle Modification with Second- Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities.Curr Obes Rep. Dec 2023;12(4):453-473. doi:10.1007/s13679-023-00534-z 281. Dalle Grave R. The Benefit of Healthy Lifestyle in the Era of New Medications to Treat Obesity. Diabetes Metab Syndr Obes. 2024;17:227-230. doi:10.2147/dmso.S447582 282. Murphy E, Finucane FM. Structured lifestyle modification as an adjunct to obesity pharmacotherapy: there is much to learn. Int J Obes (Lond). Mar 2025;49(3):427-432. doi:10.1038/s41366-024-01499-2 283. Rebello CJ, O'Neil PM, Horn DB, Greenway FL. Timing the discussion of antiobesity medications during obesity treatment. Obesity (Silver Spring). Oct 2016;24(10):2027-8. doi:10.1002/oby.21614 284. Tronieri JS, Ghanbari E, Chevinsky J, et al. Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial. Nat Med. May 2025;31(5):1653-1660. doi:10.1038/s41591-025-03556-3 285. Gilbert O, Gulati M, Gluckman TJ, et al. 2025 Concise Clinical Guidance: An ACC Expert Consensus Statement on Medical Weight Management for Optimization of Cardiovascular Health: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. Jun 16 2025;doi:10.1016/j.jacc.2025.05.024 286. Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults with Overweight or Obesity: The STEP 4 Randomized Clinical Trial. Article. JAMA - Journal of the American Medical Association. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224 287. Jastreboff AM, le Roux CW, Stefanski A, et al. Tirzepatide for Obesity Treatment and Diabetes Prevention. Article in Press. The New England journal of medicine. 2024;doi:10.1056/NEJMoa2410819 ### Page 202 288. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. Aug 2022;24(8):1553-1564. doi:10.1111/dom.14725 289. Wing RRH, James O. The National Weight Control Registry.[http://www.nwcr.ws/](http://www.nwcr.ws/) 290. Dorneles G, Algeri E, Lauterbach G, Pereira M, Fernandes B. Efficacy and Safety of Once-Weekly Subcutaneous Semaglutide in Overweight or Obese Adults: A Systematic Review with Meta-Analysis. Article. Experimental and Clinical Endocrinology and Diabetes. 2024;132(6):316-327. doi:10.1055/a-2303-8558 291. Liu L, Shi H, Xie M, Sun Y, Nahata MC. Efficacy and safety of tirzepatide versus placebo in overweight or obese adults without diabetes: a systematic review and meta-analysis of randomized controlled trials. Article in Press. International Journal of Clinical Pharmacy. 2024;doi:10.1007/s11096-024-01779-x 292. Knop FK, Aroda VR, do Vale RD, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo- controlled, phase 3 trial. Article. The Lancet. 2023;402(10403):705-719. doi:10.1016/S0140-6736(23)01185-6 293. novoMEDLINK. Semaglutide (WEGOVY) Prescribing Information.[https://www.novomedlink.com/obesity/products/treatments/wegovy/pi.html](https://www.novomedlink.com/obesity/products/treatments/wegovy/pi.html) 294. Lilly. Tirzepatide (ZEPBOUND) Prescribing Information. Tirzepatide (ZEPBOUND) Prescribing information online. Lilly. Feb 2025 295. Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: A joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Obesity (Silver Spring). Aug 2025;33(8):1475-1503. doi:10.1002/oby.24336 296. Ebrahimi P, Batlle JC, Ayati A, et al. Suicide and Self-Harm Events With GLP-1 Receptor Agonists in Adults With Diabetes or Obesity: A Systematic Review and Meta-Analysis.JAMA Psychiatry. Mar 19 2025;doi:10.1001/jamapsychiatry.2025.0091 297. Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double- dummy, placebo-controlled, phase 3 trial. Lancet. Mar 13 2021;397(10278):971-984. doi:10.1016/s0140-6736(21)00213-0 298. Hunter Gibble T, Cao D, Zhang XM, Xavier NA, Poon JL, Fitch A. Tirzepatide Was Associated with Improved Health-Related Quality of Life in Adults with Obesity or Overweight and Type 2 Diabetes: Results from the Phase 3 SURMOUNT-2 Trial. Diabetes Ther. May 2025;16(5):977-991. doi:10.1007/s13300-025-01723-w 299. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. Sep 21 2023;389(12):1069-1084. doi:10.1056/NEJMoa2306963 300. Packer M, Zile MR, Kramer CM, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. Jan 30 2025;392(5):427-437. doi:10.1056/NEJMoa2410027 301. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. Dec 14 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563 302. Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. Oct 3 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881 303. Rodriguez PJ, Zhang V, Gratzl S, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Netw Open. Jan 2 2025;8(1):e2457349. doi:10.1001/jamanetworkopen.2024.57349 ### Page 203 304. Lin Q, Xue Y, Zou H, Ruan Z, Ung COL, Hu H. Efficacy and safety of liraglutide for obesity and people who are overweight: a systematic review and meta-analysis of randomized controlled trials. Article. Expert Review of Clinical Pharmacology. 2022;15(12):1461-1469. doi:10.1080/17512433.2022.2130760 305. Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. Lancet. Apr 6 2024;403(10434):e21-e31. doi:10.1016/s0140-6736(24)00351-9 306. Khera R, Murad MH, Chandar AK, et al. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A systematic Review and Meta-analysis.JAMA. Jun 14 2016;315(22):2424-34. doi:10.1001/jama.2016.7602 307. le Roux CW, Astrup A, Fujioka K, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. Apr 8 2017;389(10077):1399-1409. doi:10.1016/s0140-6736(17)30069-7 308. Wadden TA, Tronieri JS, Sugimoto D, et al. Liraglutide 3.0 mg and Intensive Behavioral Therapy (IBT) for Obesity in Primary Care: The SCALE IBT Randomized Controlled Trial. Article. Obesity. 2020;28(3):529-536. doi:10.1002/oby.22726 309. Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. Feb 2012;95(2):297-308. doi:10.3945/ajcn.111.024927 310. Buse JB, Bain SC, Mann JFE, et al. Cardiovascular Risk Reduction With Liraglutide: An Exploratory Mediation Analysis of the LEADER Trial. Diabetes Care. Jul 2020;43(7):1546- 1552. doi:10.2337/dc19-2251 311. Blackman A, Foster GD, Zammit G, et al. Effect of liraglutide 3.0 mg in individuals withobesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes (Lond). Aug 2016;40(8):1310-9. doi:10.1038/ijo.2016.52 312. Khera R, Pandey A, Chandar AK, et al. Effects of Weight-Loss Medications on Cardiometabolic Risk Profiles: A systematic Review and Network Meta-analysis.Gastroenterology. Apr 2018;154(5):1309-1319 e7. doi:10.1053/j.gastro.2017.12.024 313. Suplicy H, Boguszewski CL, dos Santos CM, do Desterro de Figueiredo M, Cunha DR, Radominski R. A comparative study of five centrally acting drugs on the pharmacological treatment of obesity. Int J Obes (Lond). Aug 2014;38(8):1097-103. doi:10.1038/ijo.2013.225 314. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. Jul 15 2010;363(3):245-56. doi:10.1056/NEJMoa0909809 315. Siebenhofer A, Jeitler K, Horvath K, et al. Long-term effects of weight-reducing drugs in people with hypertension. Cochrane Database Syst Rev. Mar 2 2016;3:CD007654. doi:10.1002/14651858.CD007654.pub4 316. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA. Aug 18 2015;314(7):687-99. doi:10.1001/jama.2015.9676 317. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. Apr 16 2011;377(9774):1341-52. doi:10.1016/s0140-6736(11)60205-5 318. Bohula EA, Wiviott SD, McGuire DK, et al. Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med. Sep 20 2018;379(12):1107-1117. doi:10.1056/NEJMoa1808721 ### Page 204 319. O'Neil PM, Smith SR, Weissman NJ, et al. Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study. Obesity (Silver Spring). Jul 2012;20(7):1426-36. doi:10.1038/oby.2012.66 320. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. Jan 2004;27(1):155-61. doi:10.2337/diacare.27.1.155 321. Xie Z, Zheng G, Liang Z, Li M, Deng W, Cao W. Seven glucagon-like peptide-1 receptor agonists and polyagonists for weight loss in patients with obesity or overweight: an updated systematic review and network meta-analysis of randomized controlled trials. Article. Metabolism: Clinical and Experimental. 2024;161doi:10.1016/j.metabol.2024.156038 322. Wong HJ, Lin NHY, Teo YH, et al. Anti-diabetic effects of GLP-1 receptor agonists on obese and overweight patients across diabetes status, administration routes, treatment duration and baseline characteristics: A systematic review. Article in Press. Diabetes, Obesity and Metabolism. 2024;doi:10.1111/dom.16136 323. Armstrong MJ, Okanoue T, Sundby Palle M, Sejling AS, Tawfik M, Roden M. Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction-associated steatotic liver disease: Post hoc analysis of three randomised controlled trials. Article in Press. Diabetes, Obesity and Metabolism. 2024;doi:10.1111/dom.16065 324. Bancks MP, Chen H, Balasubramanyam A, et al. Type 2 Diabetes Subgroups, Risk for Complications, and Differential Effects Due to an Intensive Lifestyle Intervention. Article.Diabetes Care. 2021;44(5):1203-1210. doi:10.2337/DC20-2372 325. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. Nov 10 2016;375(19):1834-1844. doi:10.1056/NEJMoa1607141 326. Husain M, Birkenfeld AL, Donsmark M, et al. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. Aug 29 2019;381(9):841-851. doi:10.1056/NEJMoa1901118 327. McGuire DK, Marx N, Mulvagh SL, et al. Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. N Engl J Med. May 29 2025;392(20):2001-2012. doi:10.1056/NEJMoa2501006 328. NCI Dictionary of Cancer Terms. NIH. Accessed December 11, 2019,[https://www.cancer.gov/publications/dictionaries/cancer-terms/def/nutraceutical](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/nutraceutical) 329. Huang LH, Liu CY, Wang LY, Huang CJ, Hsu CH. Effects of green tea extract on overweight and obese women with high levels of low density-lipoprotein-cholesterol (LDL- C): a randomised, double-blind, and cross-over placebo-controlled clinical trial. BMC Complement Altern Med. Nov 6 2018;18(1):294. doi:10.1186/s12906-018-2355-x 330. Mousavi SM, Milajerdi A, Varkaneh HK, Gorjipour MM, Esmaillzadeh A. The effects of curcumin supplementation on body weight, body mass index and waist circumference: a systematic review and dose-response meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. Oct 29 2018:1-10. doi:10.1080/10408398.2018.1517724 331. Tripathy P, Karmahapatra P, Palaniyamma D. "RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED CLINICAL STUDY TO EVALUATE THE EFFECTS OF GARCINIA CAPLETS IN OBESE SUBJECTS" International Research Journal of Pharmacy. 2013; 332. Chen W, Liu Y, Yang Q, et al. The Effect of Protein-Enriched Meal Replacement on Waist Circumference Reduction among Overweight and Obese Chinese with Hyperlipidemia. J Am Coll Nutr. 2016;35(3):236-44. doi:10.1080/07315724.2014.989625 ### Page 205 333. Nabi BN, Sedighinejad A, Haghighi M, et al. The Anti-Obesity Effects of Green Tea: A Controlled, Randomized, Clinical Trial. Iranian Red Crescent Medical Journal. 2018;20(1) 334. Grube B, Chong WF, Chong PW, Riede L. Weight reduction and maintenance with IQP- PV-101: a 12-week randomized controlled study with a 24-week open label period.Obesity (Silver Spring). Mar 2014;22(3):645-51. doi:10.1002/oby.20577 335. Suzumura EA, Bersch-Ferreira AC, Torreglosa CR, et al. Effects of oral supplementation with probiotics or synbiotics in overweight and obese adults: a systematic review and meta-analyses of randomized trials. Nutr Rev. Jun 1 2019;77(6):430-450. doi:10.1093/nutrit/nuz001 336. Khazaal FAK, Mosah HA, Sahib H, Hamdi AS. Effect of raspberry ketones and l-carnitine on oxidative stress and body weight in Iraqi obese patients. International Journal of Pharmaceutical Sciences Review and Research. 01/01 2015;31:69-75. 337. Dara L, Hewett J, Lim JK. Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol. Dec 7 2008;14(45):6999-7004. doi:10.3748/wjg.14.6999 338. Araujo JL, Worman HJ. Acute liver injury associated with a newer formulation of the herbal weight loss supplement Hydroxycut. BMJ Case Rep. May 6 2015;2015doi:10.1136/bcr- 2015-210303 339. Morris CA, Avorn J. Internet marketing of herbal products. Jama. Sep 17 2003;290(11):1505-9. doi:10.1001/jama.290.11.1505 340. Wallace TC, Koturbash I. DSHEA 1994 - Celebrating 30 Years of Dietary Supplement Regulation in the United States. J Diet Suppl. 2025;22(1):1-8. doi:10.1080/19390211.2024.2419434 341. Lucas E, Simmons O, Tchang B, Aronne L. Pharmacologic management of weight regain following bariatric surgery. Front Endocrinol (Lausanne). 2022;13:1043595. doi:10.3389/fendo.2022.1043595 342. Golzarand M, Toolabi K, Mirmiran P. Obesity medications in patients with recurrent weight gain or suboptimal clinical response following bariatric surgery: a meta-analysis. Int J Obes (Lond). May 17 2025;doi:10.1038/s41366-025-01807-4 343. Nie Y, Zhang Y, Liu B, Meng H. Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Suboptimal Initial Clinical Response and Weight Gain Recurrence After Bariatric Surgery: a Systematic Review and Meta-analysis. Obes Surg. Mar 2025;35(3):808-822. doi:10.1007/s11695-025-07733-8 344. Agency for Health Research and Quality. The Effective Health Care Program stakeholder guide Appendix D: Research questions & PICO(TS) 2011.[https://www.ahrq.gov/research/findings/evidence-based-reports/stakeholderguide/appendixc.html](https://www.ahrq.gov/research/findings/evidence-based-reports/stakeholderguide/appendixc.html) 345. Procedure Manual Appendix VI. Criteria for Assessing Internal Validity of Individual Studies (2017). 346. Blackburn H, Jacobs D, Jr. Commentary: Origins and evolution of body mass index (BMI): continuing saga. Int J Epidemiol. Jun 2014;43(3):665-9. doi:10.1093/ije/dyu061 347. Flegal KM. Use and Misuse of BMI Categories. AMA J Ethics. Jul 1 2023;25(7):E550-558. doi:10.1001/amajethics.2023.550 348. Spahillari A, Mukamal KJ, DeFilippi C, et al. The association of lean and fat mass with all- cause mortality in older adults: The Cardiovascular Health Study. Nutr Metab Cardiovasc Dis. Nov 2016;26(11):1039-1047. doi:10.1016/j.numecd.2016.06.011 349. Conte C, Hall KD, Klein S. Is Weight Loss-Induced Muscle Mass Loss Clinically Relevant?Jama. Jul 2 2024;332(1):9-10. doi:10.1001/jama.2024.6586 350. Fabricatore AN, Wadden TA, Moore RH, Butryn ML, Heymsfield SB, Nguyen AM. Predictors of attrition and weight loss success: Results from a randomized controlled trial.Behav Res Ther. Aug 2009;47(8):685-91. doi:10.1016/j.brat.2009.05.004 ### Page 206 351. Wadden TA, Chao AM, Machineni S, et al. Author Correction: Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial(Nature Medicine, 10.1038/s41591-023-02597-w). Erratum. Nature Medicine. 2024;30(6):1784. doi:10.1038/s41591-024-02883-1 352. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. Article. New England Journal of Medicine. 2023;389(12):1069-1084. doi:10.1056/NEJMoa2306963 353. Dietetics AoNa. Adult Weight Management (AWM) Guideline (2014). 2014.[http://andeal.org/topic.cfm?menu=5276&cat=4688](http://andeal.org/topic.cfm?menu=5276&cat=4688) 354. Morgan-Bathke M, Raynor HA, Baxter SD, et al. Medical Nutrition Therapy Interventions Provided by Dietitians for Adult Overweight and Obesity Management: An Academy of Nutrition and Dietetics Evidence-Based Practice Guideline. J Acad Nutr Diet. Mar 2023;123(3):520-545.e10. doi:10.1016/j.jand.2022.11.014 355. Raynor HA, Morgan-Bathke M, Baxter SD, et al. Position of the Academy of Nutrition and Dietetics: Medical Nutrition Therapy Behavioral Interventions Provided by Dietitians for Adults With Overweight or Obesity, 2024. J Acad Nutr Diet. Mar 2024;124(3):408-415. doi:10.1016/j.jand.2023.11.013 356. Cancello R, Soranna D, Brunani A, et al. Analysis of Predictive Equations for Estimating Resting Energy Expenditure in a Large Cohort of Morbidly Obese Patients. Front Endocrinol (Lausanne). 2018;9:367. doi:10.3389/fendo.2018.00367 357. Managing Overweight and Obesity in Adults: systematic Evidence Review from the Obesity Expert Panel. National Heart Lung and Blood Institute. Accessed October 8, 2019,[https://www.nhlbi.nih.gov/health-topics/managing-overweight-obesity-in-adults](https://www.nhlbi.nih.gov/health-topics/managing-overweight-obesity-in-adults) 358. U.S. Department of Agriculture. DRI Calculator for Healthcare Professionals.[https://www.nal.usda.gov/human-nutrition-and-food-safety/dri-calculator](https://www.nal.usda.gov/human-nutrition-and-food-safety/dri-calculator) 359. Office of Disease Prevention and Health Promotion. Dietary Guidelines for Americans, 2020–2025. 9th edition, ed2020. p. 35. 360. Jakicic JM, Apovian CM, Barr-Anderson DJ, et al. Physical Activity and Excess Body Weight and Adiposity for Adults. American College of Sports Medicine Consensus Statement. Med Sci Sports Exerc. Oct 1 2024;56(10):2076-2091. doi:10.1249/mss.0000000000003520 361. Wang Z, Ying Z, Bosy-Westphal A, et al. Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure.Am J Clin Nutr. Dec 2010;92(6):1369-77. doi:10.3945/ajcn.2010.29885 362. von Loeffelholz C, Birkenfeld AL. Non-Exercise Activity Thermogenesis in Human Energy Homeostasis. In: Feingold KR, Ahmed SF, Anawalt B, et al, eds. Endotext. MDText.com, Inc. Copyright © 2000-2025, MDText.com, Inc.; 2000. 363. Reinhardt M, Thearle MS, Ibrahim M, et al. A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction. Diabetes. Aug 2015;64(8):2859-67. doi:10.2337/db14-1881 364. Taylor M, Nagle EF, Goss FL, Rubinstein EN, Simonson A. Evaluating Energy Expenditure Estimated by Wearable Technology During Variable Intensity Activity on Female Collegiate Athletes. Int J Exerc Sci. 2018;11(7):598-608. doi:10.70252/lyxi6183 365. Le S, Wang X, Zhang T, et al. Validity of three smartwatches in estimating energy expenditure during outdoor walking and running. Front Physiol. 2022;13:995575. doi:10.3389/fphys.2022.995575 366. Isidro ML, Cordido F. Approved and Off-Label Uses of Obesity Medications, and Potential New Pharmacologic Treatment Options. Pharmaceuticals (Basel). Jan 12 2010;3(1):125- 145. doi:10.3390/ph3010125 ### Page 207 367. Moyers SB. Medications as adjunct therapy for weight loss: approved and off-label agents in use. J Am Diet Assoc. Jun 2005;105(6):948-59. doi:10.1016/j.jada.2005.03.010 368. Hendricks EJ. Off-label drugs for weight management. Diabetes Metab Syndr Obes. 2017;10:223-234. doi:10.2147/dmso.s95299 369. Ben-Menachem E, Axelsen M, Johanson EH, Stagge A, Smith U. Predictors of weight loss in adults with topiramate-treated epilepsy. Obes Res. Apr 2003;11(4):556-62. doi:10.1038/oby.2003.78 370. Kramer CK, Leitao CB, Pinto LC, Canani LH, Azevedo MJ, Gross JL. Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials. Obes Rev. May 2011;12(5):e338-47. doi:10.1111/j.1467-789X.2010.00846.x 371. Paravattil B, Wilby KJ, Turgeon R. Topiramate monotherapy for weight reduction in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes Res Clin Pract. Apr 2016;114:9-14. doi:10.1016/j.diabres.2016.02.002 372. Nourredine M, Jurek L, Auffret M, et al. Efficacy and safety of topiramate in binge eating disorder: a systematic review and meta-analysis. CNS Spectr. Oct 2021;26(5):459-467. doi:10.1017/s1092852920001613 373. McElroy SL, Kotwal R, Guerdjikova AI, et al. Zonisamide in the treatment of binge eating disorder with obesity: a randomized controlled trial. J Clin Psychiatry. Dec 2006;67(12):1897-906. doi:10.4088/jcp.v67n1209 374. Gadde KM, Kopping MF, Wagner HR, 2nd, Yonish GM, Allison DB, Bray GA. Zonisamide for weight reduction in obese adults: a 1-year randomized controlled trial. Archives of internal medicine. Nov 12 2012;172(20):1557-64. doi:10.1001/2013.jamainternmed.99 375. Ghandi S, Aflatoonian A, Tabibnejad N, Moghaddam MH. The effects of metformin or orlistat on obese women with polycystic ovary syndrome: a prospective randomized open- label study. J Assist Reprod Genet. Jul 2011;28(7):591-6. doi:10.1007/s10815-011-9564-2 376. Anwary SA, Alfazzaman M, Bari N, Islam MR. Outcome of metformin treatment in polycystic ovary syndrome. Mymensingh Med J. Jan 2012;21(1):60-5. 377. Ladson G, Dodson WC, Sweet SD, et al. The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study. Fertil Steril. Mar 1 2011;95(3):1059-66 e1-7. doi:10.1016/j.fertnstert.2010.12.002 378. Meneghini LF, Orozco-Beltran D, Khunti K, et al. Weight beneficial treatments for type 2 diabetes. J Clin Endocrinol Metab. Nov 2011;96(11):3337-53. doi:10.1210/jc.2011-1074 379. Swislocki AL, Siegel D, Jialal I. Pharmacotherapy for the metabolic syndrome. Curr Vasc Pharmacol. Mar 2012;10(2):187-205. 380. Bjorkhem-Bergman L, Asplund AB, Lindh JD. Metformin for weight reduction in non- diabetic patients on antipsychotic drugs: a systematic review and meta-analysis. J Psychopharmacol. Mar 2011;25(3):299-305. doi:10.1177/0269881109353461 381. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care. Apr 2012;35(4):731-7. doi:10.2337/dc11-1299 382. Levri KM, Slaymaker E, Last A, et al. Metformin as treatment for overweight and obese adults: a systematic review. Ann Fam Med. Sep-Oct 2005;3(5):457-61. doi:10.1370/afm.343 383. Shyangdan DS, Royle P, Clar C, Sharma P, Waugh N, Snaith A. Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. Oct 5 2011;(10):CD006423. doi:10.1002/14651858.CD006423.pub2 384. Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56- Week, Open-Label, Randomized Clinical Trial. Diabetes Care. Feb 2018;41(2):258-266. doi:10.2337/dc17-0417 ### Page 208 385. O'Neil PM, Birkenfeld AL, McGowan B, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double- blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. Aug 25 2018;392(10148):637-649. doi:10.1016/s0140-6736(18)31773-2 386. Steinberg WM, Buse JB, Ghorbani MLM, Orsted DD, Nauck MA. Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial. Diabetes Care. Jul 2017;40(7):966-972. doi:10.2337/dc16-2747 387. Clar C, Gill JA, Court R, Waugh N. Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. BMJ Open. 2012;2(5)doi:10.1136/bmjopen-2012- 001007 388. Liu XY, Zhang N, Chen R, Zhao JG, Yu P. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years. J Diabetes Complications. Nov-Dec 2015;29(8):1295-303. doi:10.1016/j.jdiacomp.2015.07.011 389. Foote C, Perkovic V, Neal B. Effects of SGLT2 inhibitors on cardiovascular outcomes.Diab Vasc Dis Res. Apr 2012;9(2):117-23. doi:10.1177/1479164112441190 390. Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O'Neil PM. Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial. Obes Res. Jul 2002;10(7):633-41. doi:10.1038/oby.2002.86 391. Apovian CM, Aronne L, Rubino D, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). May 2013;21(5):935-43. doi:10.1002/oby.20309 392. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double- blind, placebo-controlled, phase 3 trial. Lancet. Aug 21 2010;376(9741):595-605. doi:10.1016/s0140-6736(10)60888-4 393. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). Jan 2011;19(1):110-20. doi:10.1038/oby.2010.147 394. Kulak-Bejda A, Bejda G, Waszkiewicz N. Safety and efficacy of naltrexone for weight loss in adult patients - a systematic review. Arch Med Sci. 2021;17(4):940-953. doi:10.5114/aoms.2020.96908 395. Tek C, Ratliff J, Reutenauer E, Ganguli R, O'Malley SS. A randomized, double-blind, placebo-controlled pilot study of naltrexone to counteract antipsychotic-associated weight gain: proof of concept. J Clin Psychopharmacol. Oct 2014;34(5):608-12. doi:10.1097/jcp.0000000000000192 396. Zhang F, Xu S, Tang L, Pan X, Tong N. Acarbose With Comparable Glucose-Lowering but Superior Weight-Loss Efficacy to Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. Front Endocrinol (Lausanne). 2020;11:288. doi:10.3389/fendo.2020.00288 397. Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, Weyer C. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity.Diabetes Care. Sep 2008;31(9):1816-23. doi:10.2337/dc08-0029 398. Food and Drug Administration. Full Prescribing Information - VYVANSE® (lisdexamfetamine dimesylate) capsules.[https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf](https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208510lbl.pdf) 399. Kehagias I, Karamanakos SN, Argentou M, Kalfarentzos F. Randomized clinical trial of laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy for the management of patients with BMI < 50 kg/m2. Obes Surg. Nov 2011;21(11):1650-6. doi:10.1007/s11695-011-0479-x ### Page 209 400. Saad F, Haider A, Doros G, Traish A. Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obesity (Silver Spring). Oct 2013;21(10):1975-81. doi:10.1002/oby.20407 401. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. Jun 2006;91(6):1995-2010. doi:10.1210/jc.2005-2847 402. Isidori AM, Giannetta E, Greco EA, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). Sep 2005;63(3):280-93. doi:10.1111/j.1365-2265.2005.02339.x 403. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. Jul 8 2010;363(2):109-22. doi:10.1056/NEJMoa1000485 404. Vigen R, O'Donnell CI, Baron AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. Nov 6 2013;310(17):1829-36. doi:10.1001/jama.2013.280386 405. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805. doi:10.1371/journal.pone.0085805 406. Mangolim AS, Brito LAR, Nunes-Nogueira VS. Effectiveness of testosterone therapy in obese men with low testosterone levels, for losing weight, controlling obesity complications, and preventing cardiovascular events: Protocol of a systematic review of randomized controlled trials. Medicine (Baltimore). Apr 2018;97(17):e0482. doi:10.1097/md.0000000000010482 407. Knight MG, Anekwe C, Washington K, Akam EY, Wang E, Stanford FC. Weight regulation in menopause. Menopause. May 24 2021;28(8):960-965. doi:10.1097/gme.0000000000001792 408. National Center for Health Statistics. 2007-2010 Sampling Methodology.[https://wwwn.cdc.gov/Nchs/Nhanes/ContinuousNhanes/SamplingNotes.aspx?BeginYear=2007](https://wwwn.cdc.gov/Nchs/Nhanes/ContinuousNhanes/SamplingNotes.aspx?BeginYear=2007) 409. Karvonen-Gutierrez CA, Park SK, Kim C. Diabetes and Menopause. Curr Diab Rep. Apr 2016;16(4):20. doi:10.1007/s11892-016-0714-x 410. Harris JA, Benedict FG. A Biometric Study of Human Basal Metabolism. Proc Natl Acad Sci U S A. Dec 1918;4(12):370-3. doi:10.1073/pnas.4.12.370 411. Patel SR, Malhotra A, White DP, Gottlieb DJ, Hu FB. Association between reduced sleep and weight gain in women. Am J Epidemiol. Nov 15 2006;164(10):947-54. doi:10.1093/aje/kwj280 412. Franklin RM, Ploutz-Snyder L, Kanaley JA. Longitudinal changes in abdominal fat distribution with menopause. Metabolism - Clinical and Experimental. 2009;58(3):311-315. doi:10.1016/j.metabol.2008.09.030 413. Salpeter SR, Walsh JM, Ormiston TM, Greyber E, Buckley NS, Salpeter EE. Meta- analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab. Sep 2006;8(5):538-54. doi:10.1111/j.1463-1326.2005.00545.x 414. Pearce EN. Thyroid hormone and obesity. Curr Opin Endocrinol Diabetes Obes. Oct 2012;19(5):408-13. doi:10.1097/MED.0b013e328355cd6c 415. Lijesen GK, Theeuwen I, Assendelft WJ, Van Der Wal G. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis. Br J Clin Pharmacol. Sep 1995;40(3):237-43. doi:10.1111/j.1365-2125.1995.tb05779.x 416. Goodbar NH, Foushee JA, Eagerton DH, Haynes KB, Johnson AA. Effect of the human chorionic gonadotropin diet on patient outcomes. Ann Pharmacother. May 2013;47(5):e23. doi:10.1345/aph.1R755 ### Page 210 417. Gastrointestinal surgery for severe obesity. Consens Statement. Mar 25-27 1991;9(1):1- 20. 418. Eisenberg D, Shikora SA, Aarts E, et al. 2022 American Society for Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO): Indications for Metabolic and Bariatric Surgery. Surg Obes Relat Dis. Dec 2022;18(12):1345-1356. doi:10.1016/j.soard.2022.08.013 419. Kim JJ, Rogers AM, Ballem N, Schirmer B. ASMBS updated position statement on insurance mandated preoperative weight loss requirements. Surg Obes Relat Dis. Jun 2016;12(5):955-9. doi:10.1016/j.soard.2016.04.019 420. Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. Jama. Jan 4 2012;307(1):56-65. doi:10.1001/jama.2011.1914 421. Gloy VL, Briel M, Bhatt DL, et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. Bmj. Oct 22 2013;347:f5934. doi:10.1136/bmj.f5934 422. Puzziferri N, Roshek TB, 3rd, Mayo HG, Gallagher R, Belle SH, Livingston EH. Long-term follow-up after bariatric surgery: a systematic review. Jama. Sep 3 2014;312(9):934-42. doi:10.1001/jama.2014.10706 423. Adams TD, Davidson LE, Litwin SE, et al. Weight and Metabolic Outcomes 12 Years after Gastric Bypass. N Engl J Med. Sep 21 2017;377(12):1143-1155. doi:10.1056/NEJMoa1700459 424. O'Brien PE, Hindle A, Brennan L, et al. Long-Term Outcomes After Bariatric Surgery: a Systematic Review and Meta-analysis of Weight Loss at 10 or More Years for All Bariatric Procedures and a Single-Centre Review of 20-Year Outcomes After Adjustable Gastric Banding. Obes Surg. Jan 2019;29(1):3-14. doi:10.1007/s11695-018-3525-0 425. Kraljevic M, Süsstrunk J, Wölnerhanssen BK, et al. Long-Term Outcomes of Laparoscopic Roux-en-Y Gastric Bypass vs Laparoscopic Sleeve Gastrectomy for Obesity: The SM- BOSS Randomized Clinical Trial. JAMA Surg. Apr 1 2025;160(4):369-377. doi:10.1001/jamasurg.2024.7052 426. Muller-Stich BP, Senft JD, Warschkow R, et al. Surgical versus medical treatment of type 2 diabetes mellitus in nonseverely obese patients: a systematic review and meta-analysis.Ann Surg. Mar 2015;261(3):421-9. doi:10.1097/sla.0000000000001014 427. Cheng J, Gao J, Shuai X, Wang G, Tao K. The comprehensive summary of surgical versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomized controlled trials. Oncotarget. Jun 28 2016;7(26):39216-39230. doi:10.18632/oncotarget.9581 428. Khorgami Z, Shoar S, Saber AA, Howard CA, Danaei G, Sclabas GM. Outcomes of Bariatric Surgery Versus Medical Management for Type 2 Diabetes Mellitus: A meta- analysis of Randomized Controlled Trials. Obes Surg. Mar 2019;29(3):964-974. doi:10.1007/s11695-018-3552-x 429. Sheng B, Truong K, Spitler H, Zhang L, Tong X, Chen L. The Long-Term Effects of Bariatric Surgery on Type 2 Diabetes Remission, Microvascular and Macrovascular Complications, and Mortality: a systematic Review and Meta-Analysis. Obes Surg. Oct 2017;27(10):2724-2732. doi:10.1007/s11695-017-2866-4 430. Courcoulas AP, Patti ME, Hu B, et al. Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes. Jama. Feb 27 2024;331(8):654-664. doi:10.1001/jama.2024.0318 431. Reges O, Greenland P, Dicker D, et al. Association of Bariatric Surgery Using Laparoscopic Banding, Roux-en-Y Gastric Bypass, or Laparoscopic Sleeve Gastrectomy vs Usual Care Obesity Management With All-Cause Mortality. JAMA. Jan 16 2018;319(3):279-290. doi:10.1001/jama.2017.20513 ### Page 211 432. Syn NL, Cummings DE, Wang LZ, et al. Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis ofmatched cohort and prospective controlled studies with 174 772 participants. Lancet. May 15 2021;397(10287):1830-1841. doi:10.1016/s0140-6736(21)00591-2 433. Sheetz KH, Gerhardinger L, Dimick JB, Waits SA. Bariatric Surgery and Long-term Survival in Patients With Obesity and End-stage Kidney Disease. JAMA Surg. Jul 1 2020;155(7):581-588. doi:10.1001/jamasurg.2020.0829 434. Arterburn DE, Olsen MK, Smith VA, et al. Association between bariatric surgery and long- term survival. Jama. Jan 6 2015;313(1):62-70. doi:10.1001/jama.2014.16968 435. Anveden Å, Taube M, Peltonen M, et al. Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study. Gynecol Oncol. May 2017;145(2):224-229. doi:10.1016/j.ygyno.2017.02.036 436. Skubleny D, Switzer NJ, Gill RS, et al. The Impact of Bariatric Surgery on Polycystic Ovary Syndrome: a systematic Review and Meta-analysis. Obes Surg. Jan 2016;26(1):169-76. doi:10.1007/s11695-015-1902-5 437. Marczuk P, Kubisa MJ, Swiech M, et al. Effectiveness and Safety of Roux-en-Y Gastric Bypass in Elderly Patients-Systematic Review and Meta-analysis. Obes Surg. Feb 2019;29(2):361-368. doi:10.1007/s11695-018-3546-8 438. Smith ME, Bacal D, Bonham AJ, et al. Perioperative and 1-year outcomes of bariatric surgery in septuagenarians: implications for patient selection. Surg Obes Relat Dis. Oct 2019;15(10):1805-1811. doi:10.1016/j.soard.2019.08.002 439. Al-Kurd A, Grinbaum R, Mordechay-Heyn T, et al. Outcomes of Sleeve Gastrectomy in Septuagenarians. Obes Surg. Dec 2018;28(12):3895-3901. doi:10.1007/s11695-018- 3418-2 440. King WC, Hinerman AS, Belle SH, Wahed AS, Courcoulas AP. Comparison of the Performance of Common Measures of Weight Regain After Bariatric Surgery for Association With Clinical Outcomes. Jama. Oct 16 2018;320(15):1560-1569. doi:10.1001/jama.2018.14433 441. Cardoso L, Rodrigues D, Gomes L, Carrilho F. Short- and long-term mortality after bariatric surgery: A systematic review and meta-analysis. Diabetes Obes Metab. Sep 2017;19(9):1223-1232. doi:10.1111/dom.12922 442. Inaba CS, Koh CY, Sujatha-Bhaskar S, et al. One-Year Mortality after Contemporary Laparoscopic Bariatric Surgery: An Analysis of the Bariatric Outcomes Longitudinal Database. J Am Coll Surg. Jun 2018;226(6):1166-1174. doi:10.1016/j.jamcollsurg.2018.02.013 443. Campos GM, Khoraki J, Browning MG, Pessoa BM, Mazzini GS, Wolfe L. Changes in Utilization of Bariatric Surgery in the United States From 1993 to 2016. Ann Surg. Feb 2020;271(2):201-209. doi:10.1097/sla.0000000000003554 444. Robertson AGN, Wiggins T, Robertson FP, et al. Perioperative mortality in bariatric surgery: meta-analysis. Br J Surg. Aug 19 2021;108(8):892-897. doi:10.1093/bjs/znab245 445. Carter J, Chang J, Birriel TJ, et al. ASMBS position statement on preoperative patient optimization before metabolic and bariatric surgery. Surg Obes Relat Dis. Dec 2021;17(12):1956-1976. doi:10.1016/j.soard.2021.08.024 446. ASMBS'. Peri-operative management of obstructive sleep apnea. Surg Obes Relat Dis. May-Jun 2012;8(3):e27-32. doi:10.1016/j.soard.2012.03.003 447. Guzman HM, Sepulveda M, Rosso N, San Martin A, Guzman F, Guzman HC. Incidence and Risk Factors for Cholelithiasis After Bariatric Surgery. Obes Surg. Jul 2019;29(7):2110-2114. doi:10.1007/s11695-019-03760-4 448. Parikh M, Johnson JM, Ballem N. ASMBS position statement on alcohol use before and after bariatric surgery. Surg Obes Relat Dis. Feb 2016;12(2):225-30. doi:10.1016/j.soard.2015.10.085 ### Page 212 449. Mechanick JI, Apovian C, Brethauer S, et al. Clinical Practice Guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures - 2019 update: Cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, the Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists - Executive Summary. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. Dec 2019;25(12):1346-1359. doi:10.4158/gl-2019-0406 450. Sogg S, Lauretti J, West-Smith L. Recommendations for the presurgical psychosocial evaluation of bariatric surgery patients. Surg Obes Relat Dis. May 2016;12(4):731-749. doi:10.1016/j.soard.2016.02.008 451. Saltzman E, Anderson W, Apovian CM, et al. Criteria for patient selection and multidisciplinary evaluation and treatment of the weight loss surgery patient. Obes Res. Feb 2005;13(2):234-43. doi:10.1038/oby.2005.32 452. Committee SG. SAGES guideline for clinical application of laparoscopic bariatric surgery.Surgical endoscopy. Oct 2008;22(10):2281-300. doi:10.1007/s00464-008-0170-z 10.1007/s00464-008-9913-0 453. Kominiarek MA, Jungheim ES, Hoeger KM, Rogers AM, Kahan S, Kim JJ. American Society for Metabolic and Bariatric Surgery position statement on the impact of obesity and obesity treatment on fertility and fertility therapy Endorsed by the American College of Obstetricians and Gynecologists and the Obesity Society. Surg Obes Relat Dis. May 2017;13(5):750-757. doi:10.1016/j.soard.2017.02.006 454. Fisher SA, Stetson BT, Kominiarek MA. Pregnancy After Bariatric Surgery. Jama. Mar 7 2023;329(9):758-759. doi:10.1001/jama.2023.1442 455. National Institute of Diabetes and Digestive and Kidney Diseases. Types of Bariatric Surgery. National Institutes of Health.[https://www.niddk.nih.gov/health-information/weight-management/bariatric-surgery/types](https://www.niddk.nih.gov/health-information/weight-management/bariatric-surgery/types) 456. Ochner CN, Gibson C, Shanik M, Goel V, Geliebter A. Changes in neurohormonal gut peptides following bariatric surgery. Int J Obes (Lond). Feb 2011;35(2):153-66. doi:10.1038/ijo.2010.132 457. ASMBS. Bariatric Surgery Procedures. 2018; 458. Torres JC, Oca CF, Garrison RN. Gastric bypass: Roux-en-Y gastrojejunostomy from the lesser curvature. Southern medical journal. Oct 1983;76(10):1217-21. 459. Abdeen G, le Roux CW. Mechanism Underlying the Weight Loss and Complications of Roux-en-Y Gastric Bypass. Review. Obes Surg. Feb 2016;26(2):410-21. doi:10.1007/s11695-015-1945-7 460. Angrisani L, Santonicola A, Iovino P, et al. IFSO Worldwide Survey 2016: Primary, Endoluminal, and Revisional Procedures. Obes Surg. Dec 2018;28(12):3783-3794. doi:10.1007/s11695-018-3450-2 461. Ali M, El Chaar M, Ghiassi S, Rogers AM. American Society for Metabolic and Bariatric Surgery updated position statement on sleeve gastrectomy as a bariatric procedure. Surg Obes Relat Dis. Oct 2017;13(10):1652-1657. doi:10.1016/j.soard.2017.08.007 462. Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V. Bilio-pancreatic bypass for obesity: II. Initial experience in man. Br J Surg. Sep 1979;66(9):618-20. doi:10.1002/bjs.1800660906 463. Buchwald H. The evolution of metabolic/bariatric surgery. Obes Surg. Aug 2014;24(8):1126-35. doi:10.1007/s11695-014-1354-3 464. Yang P, Chen B, Xiang S, Lin XF, Luo F, Li W. Long-term outcomes of laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass for morbid obesity: Results from a ### Page 213 meta-analysis of randomized controlled trials. Surg Obes Relat Dis. Apr 2019;15(4):546- 555. doi:10.1016/j.soard.2019.02.001 465. Zhang Y, Zhao H, Cao Z, et al. A randomized clinical trial of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy for the treatment of morbid obesity in China: a 5- year outcome. Obes Surg. Oct 2014;24(10):1617-24. doi:10.1007/s11695-014-1258-2 466. Peterli R, Wölnerhanssen BK, Peters T, et al. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial. Jama. Jan 16 2018;319(3):255-265. doi:10.1001/jama.2017.20897 467. Chen SY, Stem M, Schweitzer MA, Magnuson TH, Lidor AO. Assessment of postdischarge complications after bariatric surgery: A National Surgical Quality Improvement Program analysis. Surgery. Sep 2015;158(3):777-86. doi:10.1016/j.surg.2015.04.028 468. Clapp B, Ponce J, Corbett J, et al. American Society for Metabolic and Bariatric Surgery 2022 estimate of metabolic and bariatric procedures performed in the United States. Surg Obes Relat Dis. May 2024;20(5):425-431. doi:10.1016/j.soard.2024.01.012 469. Clapp B, Corbett J, Jordan M, Portela R, Ghanem OM. Single-anastomosis duodenoileal bypass with sleeve in the United States: a first comparative safety analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. Surg Obes Relat Dis. Jan 2023;19(1):11-17. doi:10.1016/j.soard.2022.08.016 470. Ghiassi S, Nimeri A, Aleassa EM, Grover BT, Eisenberg D, Carter J. American Society for Metabolic and Bariatric Surgery position statement on one-anastomosis gastric bypass.Surg Obes Relat Dis. Apr 2024;20(4):319-335. doi:10.1016/j.soard.2023.11.003 471. De Luca M, Piatto G, Merola G, et al. IFSO Update Position Statement on One Anastomosis Gastric Bypass (OAGB). Obes Surg. Jul 2021;31(7):3251-3278. doi:10.1007/s11695-021-05413-x 472. Livingston EH, Huerta S, Arthur D, Lee S, De Shields S, Heber D. Male gender is a predictor of morbidity and age a predictor of mortality for patients undergoing gastric bypass surgery. Ann Surg. Nov 2002;236(5):576-82. doi:10.1097/00000658-200211000- 00007 473. Livingston EH. Procedure incidence and in-hospital complication rates of bariatric surgery in the United States. American journal of surgery. Aug 2004;188(2):105-10. doi:10.1016/j.amjsurg.2004.03.001 474. Melinek J, Livingston E, Cortina G, Fishbein MC. Autopsy findings following gastric bypass surgery for morbid obesity. Archives of pathology & laboratory medicine. Sep 2002;126(9):1091-5. doi:10.1043/0003-9985(2002)126<1091:affgbs>2.0.co;2 475. Lancaster RT, Hutter MM. Bands and bypasses: 30-day morbidity and mortality of bariatric surgical procedures as assessed by prospective, multi-center, risk-adjusted ACS-NSQIP data. Surgical endoscopy. Dec 2008;22(12):2554-63. doi:10.1007/s00464-008-0074-y 476. Nelson DW, Blair KS, Martin MJ. Analysis of obesity-related outcomes and bariatric failure rates with the duodenal switch vs gastric bypass for morbid obesity. Archives of surgery (Chicago, Ill : 1960). Sep 2012;147(9):847-54. doi:10.1001/archsurg.2012.1654 477. Castaneda D, Popov VB, Wander P, Thompson CC. Risk of Suicide and Self-harm Is Increased After Bariatric Surgery-a systematic Review and Meta-analysis. Obes Surg. Jan 2019;29(1):322-333. doi:10.1007/s11695-018-3493-4 478. Lim RBC, Zhang MWB, Ho RCM. Prevalence of All-Cause Mortality and Suicide among Bariatric Surgery Cohorts: A Meta-Analysis. Int J Environ Res Public Health. Jul 18 2018;15(7)doi:10.3390/ijerph15071519 479. Müller A, Claes L, Smits D, Schag K, de Zwaan M. Lifetime Self-Harm Behaviors Are Not More Prevalent in Bariatric Surgery Candidates than in Community Controls with Obesity.Obes Facts. 2018;11(2):109-115. doi:10.1159/000486484 ### Page 214 480. Hung A, Maciejewski ML, Berkowitz TSZ, et al. Bariatric Surgery and Suicide Risk in Patients With Obesity. Ann Surg. Oct 1 2023;278(4):e760-e765. doi:10.1097/sla.0000000000005825 481. Müller A, Hase C, Pommnitz M, de Zwaan M. Depression and Suicide After Bariatric Surgery. Curr Psychiatry Rep. Aug 13 2019;21(9):84. doi:10.1007/s11920-019-1069-1 482. Varban OA, Cassidy RB, Sheetz KH, et al. Technique or technology? Evaluating leaks after gastric bypass. Surg Obes Relat Dis. Feb 2016;12(2):264-72. doi:10.1016/j.soard.2015.07.013 483. Altieri MS, Rogers A, Afaneh C, et al. Bariatric emergencies for the general surgeon. Surg Obes Relat Dis. May 2023;19(5):421-433. doi:10.1016/j.soard.2023.02.007 484. Podnos YD, Jimenez JC, Wilson SE, Stevens CM, Nguyen NT. Complications After Laparoscopic Gastric Bypass: A Review of 3464 Cases. Archives of Surgery. 2003;138(9):957-961. doi:10.1001/archsurg.138.9.957 485. Kollmann L, Gruber M, Lock JF, Germer CT, Seyfried F. Clinical Management of Major Postoperative Bleeding After Bariatric Surgery. Obes Surg. Mar 2024;34(3):751-759. doi:10.1007/s11695-023-07040-0 486. Csendes A, Burgos AM, Altuve J, Bonacic S. Incidence of marginal ulcer 1 month and 1 to 2 years after gastric bypass: a prospective consecutive endoscopic evaluation of 442 patients with morbid obesity. Obes Surg. Feb 2009;19(2):135-138. doi:10.1007/s11695- 008-9588-6 487. Parikh A, Alley JB, Peterson RM, et al. Management options for symptomatic stenosis after laparoscopic vertical sleeve gastrectomy in the morbidly obese. Surgical endoscopy. Mar 2012;26(3):738-46. doi:10.1007/s00464-011-1945-1 488. Clapp B, Abi Mosleh K, Corbett J, et al. Early Bowel Obstruction after Bariatric Surgery: An Analysis of the 2020-2021 MBSAQIP Database. Surg Laparosc Endosc Percutan Tech. Oct 1 2023;33(5):499-504. doi:10.1097/sle.0000000000001227 489. Winegar DA, Sherif B, Pate V, DeMaria EJ. Venous thromboembolism after bariatric surgery performed by Bariatric Surgery Center of Excellence Participants: analysis of the Bariatric Outcomes Longitudinal Database. Surg Obes Relat Dis. Mar-Apr 2011;7(2):181- 8. doi:10.1016/j.soard.2010.12.008 490. Carlin AM, Varban OA, Ehlers AP, Bonham AJ, Ghaferi AA, Finks JF. Independent predictors and timing of portomesenteric vein thrombosis after bariatric surgery. Surg Obes Relat Dis. Dec 2022;18(12):1385-1391. doi:10.1016/j.soard.2022.07.016 491. Lupoli R, Lembo E, Saldalamacchia G, Avola CK, Angrisani L, Capaldo B. Bariatric surgery and long-term nutritional issues. World J Diabetes. Nov 15 2017;8(11):464-474. doi:10.4239/wjd.v8.i11.464 492. Heber D, Greenway FL, Kaplan LM, Livingston E, Salvador J, Still C. Endocrine and nutritional management of the post-bariatric surgery patient: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. Nov 2010;95(11):4823-43. doi:10.1210/jc.2009-2128 493. Mechanick JI, Apovian C, Brethauer S, et al. Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures - 2019 Update: Cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic and Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Obesity (Silver Spring). Apr 2020;28(4):O1-O58. doi:10.1002/oby.22719 494. Cornier MA, Després JP, Davis N, et al. Assessing adiposity: a scientific statement from the American Heart Association. Circulation. Nov 1 2011;124(18):1996-2019. doi:10.1161/CIR.0b013e318233bc6a ### Page 215 495. Fosbøl M, Zerahn B. Contemporary methods of body composition measurement. Clin Physiol Funct Imaging. Mar 2015;35(2):81-97. doi:10.1111/cpf.12152 496. Ceniccola GD, Castro MG, Piovacari SMF, et al. Current technologies in body composition assessment: advantages and disadvantages. Nutrition. Jun 2019;62:25-31. doi:10.1016/j.nut.2018.11.028 497. Busetto L, Dicker D, Frühbeck G, et al. A new framework for the diagnosis, staging and management of obesity in adults. Nat Med. Sep 2024;30(9):2395-2399. doi:10.1038/s41591-024-03095-3 498. Sharma AM, Kushner RF. A proposed clinical staging system for obesity. Int J Obes (Lond). Mar 2009;33(3):289-95. doi:10.1038/ijo.2009.2 499. American Association of Clinical Endocrinology. AACE Comprehensive Type 2 Diabetes Management Algorithm. 2020.[https://pro.aace.com/pdfs/diabetes/AACE_2019_Diabetes_Algorithm_03.2021.pdf](https://pro.aace.com/pdfs/diabetes/AACE_2019_Diabetes_Algorithm_03.2021.pdf) 500. Atlantis E, Sahebolamri M, Cheema BS, Williams K. Usefulness of the Edmonton Obesity Staging System for stratifying the presence and severity of weight-related health problems in clinical and community settings: A rapid review of observational studies. Obes Rev. Nov 2020;21(11):e13120. doi:10.1111/obr.13120 501. Padwal RS, Pajewski NM, Allison DB, Sharma AM. Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. Cmaj. Oct 4 2011;183(14):E1059-66. doi:10.1503/cmaj.110387 502. Canning KL, Brown RE, Wharton S, Sharma AM, Kuk JL. Edmonton Obesity Staging System Prevalence and Association with Weight Loss in a Publicly Funded Referral- Based Obesity Clinic. J Obes. 2015;2015:619734. doi:10.1155/2015/619734 503. Frankenfield DC, Rowe WA, Cooney RN, Smith JS, Becker D. Limits of body mass index to detect obesity and predict body composition. Nutrition. Jan 2001;17(1):26-30. 504. LeBlanc E, O'Connor E, Whitlock EP, Patnode C, Kapka T. Screening for and management of obesity and overweight in adults. Evidence Report No. 89. AHRQ Publication No. 11-05159-EF-1 ed. Rockville, MD: Agency for Healthcare Research and Quality; 2011. 505. Centers for Disease Control and Prevention. Healthy Weight; 506. Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta- analysis. Obes Rev. Mar 2012;13(3):275-86. doi:10.1111/j.1467-789X.2011.00952.x 507. Abdi Dezfouli R, Mohammadian Khonsari N, Hosseinpour A, Asadi S, Ejtahed HS, Qorbani M. Waist to height ratio as a simple tool for predicting mortality: a systematic review and meta-analysis. Int J Obes (Lond). Dec 2023;47(12):1286-1301. doi:10.1038/s41366-023-01388-0 508. Cao Q, Yu S, Xiong W, et al. Waist-hip ratio as a predictor of myocardial infarction risk: A systematic review and meta-analysis. Medicine (Baltimore). Jul 2018;97(30):e11639. doi:10.1097/md.0000000000011639 509. Jeong S, Bonner R, Firari A, Kurti S, Saunders MJ, Womack CJ. The effect of acute hydration on body composition assessed by multi-frequency and single-frequency bioelectrical impedance. J Sports Med Phys Fitness. Oct 2023;63(10):1069-1074. doi:10.23736/s0022-4707.23.14913-9 510. Combest TM, Khan J, Tufano JJ, et al. Comparison of Four Body Composition Methods: Circumference Measurements, Eight-Point Bioelectrical Impedance Analysis up to 500and 1000 kHz to Dual-Energy X-Ray Absorptiometry to Measure Body Fat Percentage. Mil Med. Feb 27 2025;190(3-4):e642-e648. doi:10.1093/milmed/usae439 511. Siedler MR, Rodriguez C, Stratton MT, et al. Assessing the reliability and cross-sectional and longitudinal validity of fifteen bioelectrical impedance analysis devices. Br J Nutr. Sep 14 2023;130(5):827-840. doi:10.1017/s0007114522003749 ### Page 216 512. Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR, Sakamoto Y. Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index. Am J Clin Nutr. Sep 2000;72(3):694-701. doi:10.1093/ajcn/72.3.694 513. Heo M, Faith MS, Pietrobelli A, Heymsfield SB. Percentage of body fat cutoffs by sex, age, and race-ethnicity in the US adult population from NHANES 1999-2004. Am J Clin Nutr. Mar 2012;95(3):594-602. doi:10.3945/ajcn.111.025171 514. Colditz GA, Dart H. Chapter 1: Epidemiology and Health and Economic Consequences of Obesity. In: Wadden TA, Bray GA, eds. Handbook of Obesity Treatment: Second Edition. 2 ed. Guilford Press; 2018:3-23:chap 1. 515. Puhl RM, Pearl RL. Psychosocial Contributors to and Consequences of Obesity.Handbook of Obesity Treatment. 2018:149. 516. Rubino F, Cummings DE, Eckel RH, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. Mar 2025;13(3):221-262. doi:10.1016/s2213- 8587(24)00316-4 517. U.S. Department of Defense. Strengthening Food Security in the Force: Building on Our Progress[https://download.militaryonesource.mil/12038/MOS/Economic-Security/strengthening-food-security-in-the-force-strategy-and-roadmap-2023.pdf](https://download.militaryonesource.mil/12038/MOS/Economic-Security/strengthening-food-security-in-the-force-strategy-and-roadmap-2023.pdf) 518. United States Government Accountability Office. DOD FOOD Program; Additional Actions Needed to Implement, Oversee, and Evaluate Nutrition Efforts for Service Members[https://www.gao.gov/assets/gao-24-106155.pdf](https://www.gao.gov/assets/gao-24-106155.pdf) 519. Tong PK, Asch BJ, Rennane S. Military Compensation and Food Insecurity: Analysis in Support of the Fourteenth Quadrennial Review of Military Compensation. RAND Corporation; 2025. 520. Bray RM, Camlin CS, Fairbank JA, Dunteman GH, Wheeless SC. The Effects of Stress on Job Functioning of Military Men and Women. Armed Forces Soc. Apr 1 2001;27(3):397- 417. doi:10.1177/0095327x0102700304 521. Smith TJ, Marriott BP, Dotson L, et al. Overweight and obesity in military personnel: sociodemographic predictors. Obesity (Silver Spring). Jul 2012;20(7):1534-8. doi:10.1038/oby.2012.25 522. Gravina D, Keeler JL, Akkese MN, et al. Randomized Controlled Trials to Treat Obesity in Military Populations: A Systematic Review and Meta-Analysis. Nutrients. Nov 14 2023;15(22)doi:10.3390/nu15224778 523. Department of the Army. The Army Body Composition Program: Army Regulation 600–9.[https://www.army.mil/e2/downloads/rv7/r2/policydocs/r600_9.pdf](https://www.army.mil/e2/downloads/rv7/r2/policydocs/r600_9.pdf) 524. Department of the Navy. MARINE CORPS ORDER 6110.3A CHANGE-3[https://www.marines.mil/Portals/1/Publications/MCO%206110.3A%20W%20ADMIN%20CH-4%20(SECURED).pdf?ver=7XYc4AD_PjViwRYVmHjkpw%3d%3d](https://www.marines.mil/Portals/1/Publications/MCO%206110.3A%20W%20ADMIN%20CH-4%20(SECURED).pdf?ver=7XYc4AD_PjViwRYVmHjkpw%3d%3d) 525. Department of Defense. DoD Instruction 1308.03: DoD Physical Fitness/Body Composition Program. 2025.[https://www.esd.whs.mil/portals/54/documents/dd/issuances/dodi/130803p.pdf](https://www.esd.whs.mil/portals/54/documents/dd/issuances/dodi/130803p.pdf) 526. Food and Drug Administration. Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction.[https://www.fda.gov/regulatory-information/search-fda-guidance-documents/obesity-and-overweight-developing-drugs-and-biological-products-weight-reduction](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/obesity-and-overweight-developing-drugs-and-biological-products-weight-reduction) 527. Neuman T, Corrado R, Banaag A, Koehlmoos TP. Utilization of antiobesity medications within the Military Health System. Obesity (Silver Spring). Oct 2024;32(10):1825-1832. doi:10.1002/oby.24097 528. Department of the Army. Army Regulation 40-3.[https://armypubs.army.mil/epubs/DR_pubs/DR_a/pdf/web/r40_3.pdf](https://armypubs.army.mil/epubs/DR_pubs/DR_a/pdf/web/r40_3.pdf) 529. Department of the Air Force. Air Force Instruction 44-102.[https://static.e-publishing.af.mil/production/1/af_sg/publication/afi44-102/afi44-102.pdf](https://static.e-publishing.af.mil/production/1/af_sg/publication/afi44-102/afi44-102.pdf) ### Page 217 530. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. Jama. Jul 18 2007;298(3):309-16. doi:10.1001/jama.298.3.309 531. Diabetes Care. 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. Jan 1 2024;47(Suppl 1):S145-s157. doi:10.2337/dc24-S008 532. Kanwal F, Neuschwander-Tetri BA, Loomba R, Rinella ME. Metabolic dysfunction- associated steatotic liver disease: Update and impact of new nomenclature on the American Association for the Study of Liver Diseases practice guidance on nonalcoholic fatty liver disease. Hepatology. May 1 2024;79(5):1212-1219. doi:10.1097/hep.0000000000000670 533. Patnode CD, Redmond N, Iacocca MO, Henninger M. Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Known Cardiovascular Disease Risk Factors: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.Jama. Jul 26 2022;328(4):375-388. doi:10.1001/jama.2022.7408 534. Mangione CM, Barry MJ, Nicholson WK, et al. Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Cardiovascular Disease Risk Factors: US Preventive Services Task Force Recommendation Statement. Jama. Jul 26 2022;328(4):367-374. doi:10.1001/jama.2022.10951 535. Prevention NCfHPaD. Eat Wisely.[https://www.prevention.va.gov/Healthy_Living/Eat_Wisely.asp](https://www.prevention.va.gov/Healthy_Living/Eat_Wisely.asp) 536. Prevention NCfHPaD. Be Physically Active.[https://www.prevention.va.gov/Healthy_Living/Be_Physically_Active.asp](https://www.prevention.va.gov/Healthy_Living/Be_Physically_Active.asp) 537. Lobelo F, Rohm Young D, Sallis R, et al. Routine Assessment and Promotion of Physical Activity in Healthcare Settings: A Scientific Statement From the American Heart Association. Circulation. May 1 2018;137(18):e495-e522. doi:10.1161/cir.0000000000000559 538. Makoul G, Clayman ML. An integrative model of shared decision making in medical encounters. Patient education and counseling. Mar 2006;60(3):301-12. doi:10.1016/j.pec.2005.06.010 539. Palmer S, Tubbs I, Whybrow A. Health coaching to facilitate the promotion of healthy behaviour and achievement of health-related goals. Int J Health Prom Eval. 2003;41(3):91- 93. 540. Whitlock EP, Orleans CT, Pender N, Allan J. Evaluating primary care behavioral counseling interventions: an evidence-based approach. American journal of preventive medicine. May 2002;22(4):267-84. 541. Goldstein MG, Whitlock EP, DePue J, Planning Committee of the Addressing Multiple Behavioral Risk Factors in Primary Care Project. Multiple behavioral risk factor interventions in primary care. Summary of research evidence. American journal of preventive medicine. Aug 2004;27(2 Suppl):61-79. doi:10.1016/j.amepre.2004.04.023 542. Rollnick S, Miller W, Butler C. Motivational interviewing in health care. The Guilford Press; 2008. 543. Miller W, Rollnick S. Motivational Interviewing: Helping People Change and Grow. 4th ed. The Guilford Press; 2023. 544. Schillinger D, Piette J, Grumbach K, et al. Closing the loop: physician communication with diabetic patients who have low health literacy. Archives of internal medicine. Jan 13 2003;163(1):83-90. 545. Levinson W, Lesser CS, Epstein RM. Developing physician communication skills for patient-centered care. Health affairs. Jul 2010;29(7):1310-8. doi:10.1377/hlthaff.2009.0450 ### Page 218 546. Puhl RM, Phelan SM, Nadglowski J, Kyle TK. Overcoming Weight Bias in the Management of Patients With Diabetes and Obesity. Clin Diabetes. Jan 2016;34(1):44-50. doi:10.2337/diaclin.34.1.44 547. Phelan SM, Burgess DJ, Yeazel MW, Hellerstedt WL, Griffin JM, van Ryn M. Impact of weight bias and stigma on quality of care and outcomes for patients with obesity. Obes Rev. Apr 2015;16(4):319-26. doi:10.1111/obr.12266 548. Albury C, Webb H, Stokoe E, et al. Relationship Between Clinician Language and the Success of Behavioral Weight Loss Interventions : A Mixed-Methods Cohort Study. Ann Intern Med. Nov 2023;176(11):1437-1447. doi:10.7326/m22-2360 549. Cole SA, Sannidhi D, Jadotte YT, Rozanski A. Using motivational interviewing and brief action planning for adopting and maintaining positive health behaviors. Prog Cardiovasc Dis. Mar-Apr 2023;77:86-94. doi:10.1016/j.pcad.2023.02.003 550. Tooley EM, Kolahi A. Motivating Behavioral Change. Med Clin North Am. Jul 2022;106(4):627-639. doi:10.1016/j.mcna.2022.01.006 551. Miller WRR, Stephen. Motivational Interviewing: Helping People Change and Grow. 2023. 552. Burke BL, Arkowitz H, Menchola M. The efficacy of motivational interviewing: a meta- analysis of controlled clinical trials. J Consult Clin Psychol. Oct 2003;71(5):843-61. doi:10.1037/0022-006X.71.5.843 553. Britt E, Hudson SM, Blampied NM. Motivational interviewing in health settings: a review.Patient education and counseling. May 2004;53(2):147-55. doi:10.1016/S0738- 3991(03)00141-1 554. Burton AM, Agne AA, Lehr SM, Davis NJ, Willett LL, Cherrington AL. Training residents in obesity counseling: incorporating principles of motivational interviewing to enhance patient centeredness. Journal of graduate medical education. Sep 2011;3(3):408-11. doi:10.4300/JGME-03-03-34 555. DiLillo V, West DS. Motivational interviewing for weight loss. The Psychiatric clinics of North America. Dec 2011;34(4):861-9. doi:10.1016/j.psc.2011.08.003 556. Hettema J, Steele J, Miller WR. Motivational interviewing. Annual review of clinical psychology. 2005;1:91-111. doi:10.1146/annurev.clinpsy.1.102803.143833 557. Levensky ER, Forcehimes A, O'Donohue WT, Beitz K. Motivational interviewing: an evidence-based approach to counseling helps patients follow treatment recommendations.The American journal of nursing. Oct 2007;107(10):50-8; quiz 58-9. doi:10.1097/01.NAJ.0000292202.06571.24 558. Williams GC, Minicucci DS, Kouides RW, et al. Self-determination, smoking, diet and health. Health education research. Oct 2002;17(5):512-21. 559. Armstrong MJ, Mottershead TA, Ronksley PE, Sigal RJ, Campbell TS, Hemmelgarn BR. Motivational interviewing to improve weight loss in overweight and/or obese patients: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. Sep 2011;12(9):709-23. doi:10.1111/j.1467-789X.2011.00892.x 560. West DS, DiLillo V, Bursac Z, Gore SA, Greene PG. Motivational interviewing improves weight loss in women with type 2 diabetes. Diabetes Care. May 2007;30(5):1081-7. doi:10.2337/dc06-1966 561. Bokhour BG, Hyde J, Kligler B, et al. From patient outcomes to system change: Evaluating the impact of VHA's implementation of the Whole Health System of Care. Health Serv Res. Jun 2022;57 Suppl 1(Suppl 1):53-65. doi:10.1111/1475-6773.13938 562. Prevention NCfHPaD. MOVE! Weight Management Program.[https://www.move.va.gov/](https://www.move.va.gov/) 563. Rosenbaum M, Hirsch J, Gallagher DA, Leibel RL. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr. Oct 2008;88(4):906-12. doi:10.1093/ajcn/88.4.906 ### Page 219 564. Knuth ND, Johannsen DL, Tamboli RA, et al. Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin.Obesity (Silver Spring). Dec 2014;22(12):2563-9. doi:10.1002/oby.20900 565. Oppert JM, Ciangura C, Bellicha A. Physical activity and exercise for weight loss and maintenance in people living with obesity. Rev Endocr Metab Disord. Oct 2023;24(5):937- 949. doi:10.1007/s11154-023-09805-5 566. Weintraub MA, D'Angelo D, Tchang BG, et al. Five-year Weight Loss Maintenance With Obesity Pharmacotherapy. J Clin Endocrinol Metab. Aug 18 2023;108(9):e832-e841. doi:10.1210/clinem/dgad100