2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T8b3,Psoriasis is a chronic immune-mediated disease associated with cardiovascular, metabolic, musculoskeletal, psychiatric, hepatic, kidney, and pulmonary comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved by the US Food and Drug Administration for type 2 diabetes, obesity, cardiovascular risk reduction, chronic kidney disease, obstructive sleep apnea, and metabolic dysfunction-associated steatohepatitis-conditions common in psoriasis. Emerging evidence suggests GLP-1 RAs and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists may improve psoriatic skin disease, partly through immune modulation. If confirmed in larger randomized clinical trials, GLP-1-based therapies may offer an opportunity to address both cutaneous disease and cardiometabolic comorbidities. This primer from the US National Psoriasis Foundation Medical Board sought to provide an evidence-informed narrative synthesis and practical considerations to introduce dermatologists to GLP-1 RAs for psoriasis treatment. GLP-1 RAs have been associated with reductions in Psoriasis Area and Severity Index (PASI) scores, particularly in patients with obesity or type 2 diabetes. Studies report relative PASI reductions ranging from approximately 40% to 80% with parallel quality-of-life gains, although most of these studies are small (7-48 patients), short term (≤6 months), and lack a control group. Semaglutide and liraglutide have been associated with reductions in C-reactive protein, interleukin-6, lipids, and visceral adiposity. In small, translational cohorts, PASI improvement has been correlated with reductions in superficial adiposity and dermal γδ T-cell density. GLP-1 RAs combine safely with methotrexate, cyclosporine, and biologics. Adverse effects are mainly transient gastrointestinal symptoms; pancreatitis and gallbladder events are rare. Early data show both metabolic and immunomodulatory benefits. This review found that GLP-1-based therapies target shared metabolic and inflammatory pathways in psoriasis. Current evidence supports consideration of adjunctive use in selected patients with metabolic comorbidities, although definitive conclusions await larger randomized clinical trials.31:Tabe, Importance Psoriasis is a chronic immune-mediated disease associated with cardiovascular, metabolic, musculoskeletal, psychiatric, hepatic, kidney, and pulmonary comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved by the US Food and Drug Administration for type 2 diabetes, obesity, cardiovascular risk reduction, chronic kidney disease, obstructive sleep apnea, and metabolic dysfunction–associated steatohepatitis—conditions common in psoriasis. Emerging evidence suggests GLP-1 RAs and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists may improve psoriatic skin disease, partly through immune modulation. If confirmed in larger randomized clinical trials, GLP-1–based therapies may offer an opportunity to address both cutaneous disease and cardiometabolic comorbidities. This primer from the US National Psoriasis Foundation Medical Board sought to provide an evidence-informed narrative synthesis and practical considerations to introduce dermatologists to GLP-1 RAs for psoriasis treatment. Observations GLP-1 RAs have been associated with reductions in Psoriasis Area and Severity Index (PASI) scores, particularly in patients with obesity or type 2 diabetes. Studies report relative PASI reductions ranging from approximately 40% to 80% with parallel quality-of-life gains, although most of these studies are small (7-48 patients), short term (≤6 months), and lack a control group. Semaglutide and liraglutide have been associated with reductions in C-reactive protein, interleukin-6, lipids, and visceral adiposity. In small, translational cohorts, PASI improvement has been correlated with reductions in superficial adiposity and dermal γδ T-cell density. GLP-1 RAs combine safely with methotrexate, cyclosporine, and biologics. Adverse effects are mainly transient gastrointestinal symptoms; pancreatitis and gallbladder events are rare. Early data show both metabolic and immunomodulatory benefits. Conclusions and Relevance This review found that GLP-1–based therapies target shared metabolic and inflammatory pathways in psoriasis. Current evidence supports consideration of adjunctive use in selected patients with metabolic comorbidities, although definitive conclusions await larger randomized clinical trials. 32:T6e9,Next-generation incretin therapies, including semaglutide and tirzepatide, have transformed obesity and Type 2 diabetes management. However, evidence-based nutritional strategies to support safe and effective use of these agents remain limited. To address this gap, we conducted a systematic scoping review across five databases of studies published between January 2015 and April 2025 to map and appraise clinical trials incorporating nutritional interventions or dietary assessments during semaglutide or tirzepatide therapy in adults with obesity or Type 2 diabetes. Eligible studies included adults receiving semaglutide or tirzepatide with either an active dietary intervention or measured nutrition-related outcomes. Study quality was assessed using established tools. Twelve studies were included: 10 randomized controlled trials, one non-randomized comparative study, and one cross-sectional observational study. Interventions ranged from structured very-low-energy or ketogenic diets to general lifestyle counseling and observational dietary assessments. Across studies, energy intake decreased by 24% to 39%, but lean tissue loss accounted for up to 40% of total weight reduction. Only three studies involved nutrition professionals, and systematic assessment of protein or micronutrient intake was rare. One observational study found widespread nutrient inadequacies and limited access to dietetic support. Despite the effectiveness of semaglutide and tirzepatide for weight loss, evidence on optimal dietary strategies is sparse. Early dietitian involvement, high-protein, nutrient-dense diets, and routine nutritional monitoring should be prioritized. Robust trials are needed to define best practice for integrating dietary care alongside pharmacotherapy.33:T740,ABSTRACT Next‐generation incretin therapies, including semaglutide and tirzepatide, have transformed obesity and Type 2 diabetes management. However, evidence‐based nutritional strategies to support safe and effective use of these agents remain limited. To address this gap, we conducted a systematic scoping review across five databases of studies published between January 2015 and April 2025 to map and appraise clinical trials incorporating nutritional interventions or dietary assessments during semaglutide or tirzepatide therapy in adults with obesity or Type 2 diabetes. Eligible studies included adults receiving semaglutide or tirzepatide with either an active dietary intervention or measured nutrition‐related outcomes. Study quality was assessed using established tools. Twelve studies were included: 10 randomized controlled trials, one non‐randomized comparative study, and one cross‐sectional observational study. Interventions ranged from structured very‐low‐energy or ketogenic diets to general lifestyle counseling and observational dietary assessments. Across studies, energy intake decreased by 24% to 39%, but lean tissue loss accounted for up to 40% of total weight reduction. Only three studies involved nutrition professionals, and systematic assessment of protein or micronutrient intake was rare. One observational study found widespread nutrient inadequacies and limited access to dietetic support. Despite the effectiveness of semaglutide and tirzepatide for weight loss, evidence on optimal dietary strategies is sparse. Early dietitian involvement, high‐protein, nutrient‐dense diets, and routine nutritional monitoring should be prioritized. Robust trials are needed to define best practice for integrating dietary care alongside pharmacotherapy.34:T4dc,There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and of the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP-1 RAs and GIP/GLP-1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body weight alongside improvements in health status and exercise capacity. Whether these effects translate into fewer HF events or lower cardiovascular mortality remains uncertain, as current evidence is limited to two small trials with few observed events. In contrast, data regarding the efficacy and safety of these drugs in HF with reduced ejection fraction are scarce, with dedicated outcome trials yet to be launched. Finally, this document highlights knowledge gaps and outlines future research directions in this field.35:T4fb,There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and of the dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP‐1 RAs and GIP/GLP‐1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body weight alongside improvements in health status and exercise capacity. Whether these effects translate into fewer HF events or lower cardiovascular mortality remains uncertain, as current evidence is limited to two small trials with few observed events. In contrast, data regarding the efficacy and safety of these drugs in HF with reduced ejection fraction are scarce, with dedicated outcome trials yet to be launched. Finally, this document highlights knowledge gaps and outlines future research directions in this field.36:T687,Of 308 included participants, 219 (71.1%) were female, 89 (28.9%) were male, and the mean (SD) age was 47.1 (12.2) years. There were 54 participants in the less than 25% weight regain group, 77 in the 25% to less than 50% group, 103 in the 50% to less than 75% group, and 74 in the 75% or more group. Baseline demographic and clinical characteristics were similar across categories. During the initial 36 weeks of tirzepatide treatment, participants' weight decreased and cardiometabolic parameters improved. After withdrawal of tirzepatide, from week 36 to week 88, the mean change in waist circumference increased by weight regain category (<25% weight regain, 0.8 cm; 95% CI, -1.0 to 2.6; 25% to <50%, 5.4 cm; 95% CI, 4.0-6.8; 50% to <75%, 10.1 cm; 95% CI, 8.9-11.3; ≥75%, 14.7 cm; 95% CI, 12.7-16.7; P < .001), as did systolic blood pressure (6.8 mm Hg [95% CI, 3.9-9.7], 7.3 mm Hg [95% CI, 4.8-9.8], 9.6 mm Hg [95% CI, 7.1-12.1], and 10.4 mm Hg [95% CI, 8.0-12.8], respectively; P = .002), non-high-density lipoprotein cholesterol (-0.4% [95% CI, -7.3 to 6.5], 1.6% [95% CI, -2.3 to 5.5], 8.4% [95% CI, 3.9-12.9], and 10.8% [95% CI, 5.3-16.3], respectively), hemoglobin A1c (0.14% [95% CI, 0.06-0.22], 0.15% [95% CI, 0.09-0.21], 0.27% [95% CI, 0.21-0.33], and 0.35% [95% CI, 0.29-0.41], respectively; P < .001), and fasting insulin (-4.0% [95% CI, -20.7 to 12.7], 15.4% [95% CI, 2.3-28.5], 46.2% [95% CI, 29.5-62.9], and 26.3% [95% CI, 9.6-43.0], respectively). Changes at week 88 in waist circumference, non-high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36.37:Tcf0,In the SURMOUNT-4 trial, most adults with obesity who had tirzepatide withdrawn following a 36-week treatment regained weight. The association between the degree of weight regain and cardiometabolic parameters after tirzepatide withdrawal is unknown. To assess changes in cardiometabolic parameters by degree of weight regain after withdrawal of tirzepatide. This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo. Data were collected from March 2021 to May 2023, and data were analyzed from February 2024 to March 2025. After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88). Changes from week 36 to week 88 in cardiometabolic parameters on tirzepatide withdrawal were assessed by the degree of weight regain at week 88 as a percentage of weight lost while receiving tirzepatide from week 0 to 36: less than 25%, 25% to less than 50%, 50% to less than 75%, and 75% or more. Of 308 included participants, 219 (71.1%) were female, 89 (28.9%) were male, and the mean (SD) age was 47.1 (12.2) years. There were 54 participants in the less than 25% weight regain group, 77 in the 25% to less than 50% group, 103 in the 50% to less than 75% group, and 74 in the 75% or more group. Baseline demographic and clinical characteristics were similar across categories. During the initial 36 weeks of tirzepatide treatment, participants' weight decreased and cardiometabolic parameters improved. After withdrawal of tirzepatide, from week 36 to week 88, the mean change in waist circumference increased by weight regain category (<25% weight regain, 0.8 cm; 95% CI, -1.0 to 2.6; 25% to <50%, 5.4 cm; 95% CI, 4.0-6.8; 50% to <75%, 10.1 cm; 95% CI, 8.9-11.3; ≥75%, 14.7 cm; 95% CI, 12.7-16.7; P < .001), as did systolic blood pressure (6.8 mm Hg [95% CI, 3.9-9.7], 7.3 mm Hg [95% CI, 4.8-9.8], 9.6 mm Hg [95% CI, 7.1-12.1], and 10.4 mm Hg [95% CI, 8.0-12.8], respectively; P = .002), non-high-density lipoprotein cholesterol (-0.4% [95% CI, -7.3 to 6.5], 1.6% [95% CI, -2.3 to 5.5], 8.4% [95% CI, 3.9-12.9], and 10.8% [95% CI, 5.3-16.3], respectively), hemoglobin A1c (0.14% [95% CI, 0.06-0.22], 0.15% [95% CI, 0.09-0.21], 0.27% [95% CI, 0.21-0.33], and 0.35% [95% CI, 0.29-0.41], respectively; P < .001), and fasting insulin (-4.0% [95% CI, -20.7 to 12.7], 15.4% [95% CI, 2.3-28.5], 46.2% [95% CI, 29.5-62.9], and 26.3% [95% CI, 9.6-43.0], respectively). Changes at week 88 in waist circumference, non-high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36. In this post hoc analysis of the SURMOUNT-4 trial, among participants with obesity who achieved weight reduction with 36-week tirzepatide treatment, withdrawing tirzepatide led to 25% or greater weight regain in most participants within 1 year and was associated with a greater reversal of their initial cardiometabolic parameter improvements compared with those who maintained weight reduction. These findings underscore the importance of continued obesity treatment. ClinicalTrials.gov Identifier: NCT04660643.38:T1440, Importance In the SURMOUNT-4 trial, most adults with obesity who had tirzepatide withdrawn following a 36-week treatment regained weight. The association between the degree of weight regain and cardiometabolic parameters after tirzepatide withdrawal is unknown. Objective To assess changes in cardiometabolic parameters by degree of weight regain after withdrawal of tirzepatide. Design, Setting, and Participants This post hoc analysis of the SURMOUNT-4 trial included tirzepatide-treated participants with 10% or greater weight reduction at week 36 initially randomized to placebo. Data were collected from March 2021 to May 2023, and data were analyzed from February 2024 to March 2025. Interventions After 36 weeks of tirzepatide treatment (maximum tolerated dose of 10 mg or 15 mg), participants were randomized 1:1 to continue tirzepatide or to switch to placebo for 52 weeks (week 36 to 88). Main Outcomes and Measures Changes from week 36 to week 88 in cardiometabolic parameters on tirzepatide withdrawal were assessed by the degree of weight regain at week 88 as a percentage of weight lost while receiving tirzepatide from week 0 to 36: less than 25%, 25% to less than 50%, 50% to less than 75%, and 75% or more. Results Of 308 included participants, 219 (71.1%) were female, 89 (28.9%) were male, and the mean (SD) age was 47.1 (12.2) years. There were 54 participants in the less than 25% weight regain group, 77 in the 25% to less than 50% group, 103 in the 50% to less than 75% group, and 74 in the 75% or more group. Baseline demographic and clinical characteristics were similar across categories. During the initial 36 weeks of tirzepatide treatment, participants’ weight decreased and cardiometabolic parameters improved. After withdrawal of tirzepatide, from week 36 to week 88, the mean change in waist circumference increased by weight regain category (&lt;25% weight regain, 0.8 cm; 95% CI, −1.0 to 2.6; 25% to &lt;50%, 5.4 cm; 95% CI, 4.0-6.8; 50% to &lt;75%, 10.1 cm; 95% CI, 8.9-11.3; ≥75%, 14.7 cm; 95% CI, 12.7-16.7; P &lt; .001), as did systolic blood pressure (6.8 mm Hg [95% CI, 3.9-9.7], 7.3 mm Hg [95% CI, 4.8-9.8], 9.6 mm Hg [95% CI, 7.1-12.1], and 10.4 mm Hg [95% CI, 8.0-12.8], respectively; P = .002), non–high-density lipoprotein cholesterol (−0.4% [95% CI, −7.3 to 6.5], 1.6% [95% CI, −2.3 to 5.5], 8.4% [95% CI, 3.9-12.9], and 10.8% [95% CI, 5.3-16.3], respectively), hemoglobin A 1c (0.14% [95% CI, 0.06-0.22], 0.15% [95% CI, 0.09-0.21], 0.27% [95% CI, 0.21-0.33], and 0.35% [95% CI, 0.29-0.41], respectively; P &lt; .001), and fasting insulin (−4.0% [95% CI, −20.7 to 12.7], 15.4% [95% CI, 2.3-28.5], 46.2% [95% CI, 29.5-62.9], and 26.3% [95% CI, 9.6-43.0], respectively). Changes at week 88 in waist circumference, non–high-density lipoprotein cholesterol, and fasting insulin in those with less than 25% weight regain were not significantly different compared with week 36. Conclusions and Relevance In this post hoc analysis of the SURMOUNT-4 trial, among participants with obesity who achieved weight reduction with 36-week tirzepatide treatment, withdrawing tirzepatide led to 25% or greater weight regain in most participants within 1 year and was associated with a greater reversal of their initial cardiometabolic parameter improvements compared with those who maintained weight reduction. These findings underscore the importance of continued obesity treatment. Trial Registration ClinicalTrials.gov Identifier: NCT04660643 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Dual GIP/GLP-1 Receptor Agonist: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Dual GIP/GLP-1 Receptor Agonist (modality). Clinician-written summaries and actionable practice insights. 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semaglutide carries multiple brand names (Wegovy, Rybelsus) across indications — clinicians should verify the specific formulation and dose per indication.","value_numeric":null},{"paper_doi":"10.1097/mnh.0000000000001225","tag_type":"warning","value":"Resmetirom's UK approval was listed as pending at time of publication (September 2026); regulatory status should be verified locally before prescribing.","value_numeric":null},{"paper_doi":"10.1097/mnh.0000000000001225","tag_type":"warning","value":"Semaglutide's UK approval for MASH was also listed as pending at publication; verify current local authorization before clinical use.","value_numeric":null},{"paper_doi":"10.1097/mnh.0000000000001225","tag_type":"warning","value":"The CRHM nomenclature used throughout is not yet consensus-endorsed by any major society; clinicians should note this framework is proposed, not official.","value_numeric":null},{"paper_doi":"10.1097/mnh.0000000000001225","tag_type":"warning","value":"This is a narrative review; evidence levels cited for individual recommendations reflect the underlying trials, which are largely single-domain RCTs not designed for CRHM multimorbidity populations. No sample size applies to the review itself.","value_numeric":null}],"summaries":{"what_studied":"This review examines the mechanistic, epidemiological, and therapeutic evidence for integrating the liver into the cardiovascular-kidney-metabolic (CKM) framework, proposing the term cardiovascular-renal-hepatic-metabolic (CRHM) syndrome. It covers pathophysiology (lipotoxicity, ectopic fat, gut-liver axis, neurohormonal activation) and recent trial data (2024–2025) across GLP-1 receptor agonists, SGLT2 inhibitors, nonsteroidal MRAs, and resmetirom.","key_result":"Coexistent MASLD and CKD confer additive, stage-dependent mortality risk exceeding either condition alone; hepatic fibrosis severity — not steatosis — is the dominant prognostic driver. Semaglutide achieved steatohepatitis resolution in 62.9% vs. 34.3% (placebo) in ESSENCE, and is now the first agent with regulatory approval across all four CRHM domains. Resmetirom became the first licensed MASH-specific therapy (FDA approval March 2024; EC authorization August 2025). Tirzepatide reduced composite CV death/worsening HF by 38% vs. placebo in HFpEF (SUMMIT).","limitations":"- All current major cardiorenal and MASH outcome trials systematically exclude the overlapping CRHM phenotype, limiting generalizability to real-world multimorbid patients.\n- No head-to-head combination therapy trial exists; the proposed multi-drug CRHM regimen is extrapolated from single-disease trials.\n- Liver-related death is a competing risk that can bias conventional time-to-event analyses in CKD/MASLD cohorts but is rarely accounted for.","practice_takeaway":"Calculate FIB-4 in any CKD patient with at least one cardiometabolic risk factor; values above 1.3 should prompt elastography-based fibrosis staging to guide both risk stratification and drug selection. For confirmed MASLD with significant fibrosis, build a regimen around ACEi/ARB + SGLT2i + GLP-1RA, adding finerenone (if T2DM, UACR >30 mg/g, eGFR ≥25) and resmetirom (if noncirrhotic F2–F3, eGFR ≥45) where criteria are met."}},{"doi":"10.1038/s41574-026-01258-5","pmid":"42168641","title":"Causes and consequences of discontinuation of GLP1RAs or tirzepatide","journal_title":"Nature Reviews Endocrinology","journal_issn":"1759-5029","published_at":"2026-05-21T00:00:00.000Z","url":"https://doi.org/10.1038/s41574-026-01258-5","source_score":17,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-23T13:24:52.421Z","updated_at":"2026-05-23T13:24:52.421Z","tags":[{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"brand","value":"Mounjaro","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"brand","value":"Zepbound","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"condition","value":"Type 2 Diabetes Mellitus","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"generic","value":"tirzepatide","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"modality","value":"Dual GIP/GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"warning","value":"Brand tags (Mounjaro, Zepbound) are inferred from tirzepatide's known approvals; they are not explicitly named in the abstract.","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"warning","value":"Hard outcome data (e.g., MACE incidence post-discontinuation) are explicitly noted as scarce; cardiovascular risk claims are largely mechanistic/inferential.","value_numeric":null},{"paper_doi":"10.1038/s41574-026-01258-5","tag_type":"warning","value":"No specific sample size is applicable — this is a narrative review, not a primary study.","value_numeric":null}],"summaries":{"what_studied":"This review examines why patients discontinue GLP-1 receptor agonists (GLP1RAs) or tirzepatide in real-world settings, and what cardiometabolic consequences follow — including weight regain, glycemic deterioration, and potential cardiovascular risk — in people with type 2 diabetes and/or overweight/obesity.","key_result":"Real-world persistence on GLP1RAs and tirzepatide is often suboptimal, with many patients stopping within the first year. Discontinuation leads to weight regain, worsening of cardiometabolic risk factors, and possible HbA1c fluctuation; the absence of anti-atherosclerotic and plaque-stabilizing effects after stopping may acutely elevate cardiovascular risk, though hard outcome data remain scarce.","limitations":"- Very few data exist on hard clinical outcomes (e.g., MACE, renal events) specifically in patients who discontinue these agents.\n- Evidence on repeated stop-start cycles and their cumulative cardiovascular/microvascular impact is largely indirect or theoretical.\n- As a narrative review, it does not provide pooled quantitative estimates or systematic risk-of-bias assessments.","practice_takeaway":"Clinicians should proactively address modifiable discontinuation drivers — GI side effects, cost, and patient expectations — to sustain therapy, since stopping GLP1RAs or tirzepatide is associated with rapid weight regain and cardiometabolic deterioration. Patients who must stop should be monitored closely for cardiovascular risk, given the potential loss of plaque-stabilizing benefits."}},{"doi":"10.1016/s2213-8587(26)00032-x","pmid":"42114520","title":"A comparison of the effects of tirzepatide and dulaglutide on major kidney events in people with type 2 diabetes: pre-specified exploratory analyses of the SURPASS-CVOT trial","journal_title":"The Lancet Diabetes & 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Twelve studies met criteria (10 randomized controlled trials, 1 non-randomized comparative study, 1 cross-sectional observational study).","key_result":"Across studies, energy intake decreased by 24%–39%, and lean tissue loss comprised up to 40% of total weight lost. Only three studies involved nutrition professionals; one observational study reported widespread nutrient inadequacies and limited access to dietetic support.","limitations":"Only 12 heterogeneous studies were included, with interventions ranging from very-low-energy/ketogenic diets to general counseling, limiting comparability. 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