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:T431,A total of 22 short-term studies comprising 10 962 participants (aripiprazole: n = 1297; brexpiprazole: n = 1973; cariprazine: n = 1894; lumateperone: n = 483; quetiapine extended release [XR]: n = 719; and placebo: n = 4596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes.31:Ta68,Most adults living with major depressive disorder (MDD) fail to achieve remission with conventional antidepressants. The US Food and Drug Administration (FDA) has approved 5 atypical antipsychotics in MDD on the basis of their substantial evidence of efficacy and safety. To compare the efficacy and acceptability of FDA-approved atypical antipsychotics for the adjunctive treatment of MDD in order to provide decision support to practitioners and persons with lived experience. A systematic search was conducted using PubMed/MEDLINE, PsycINFO, the Cochrane Library, and Embase from database inception through July 15, 2025. Six independent raters screened publications for eligibility. Inclusion criteria were atypical antipsychotics that are FDA approved in the adjunctive treatment of MDD. Two independent raters obtained data and examined risk of bias in accordance with the Cochrane criteria. Effect sizes were synthesized using random-effects models. Data were analyzed from August to September 2025. The primary outcomes were efficacy (ie, ≥50% reduction from baseline in the total Montgomery-Åsberg Depression Rating Scale [MADRS] score) and acceptability (ie, all-cause discontinuation). A total of 22 short-term studies comprising 10 962 participants (aripiprazole: n = 1297; brexpiprazole: n = 1973; cariprazine: n = 1894; lumateperone: n = 483; quetiapine extended release [XR]: n = 719; and placebo: n = 4596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes. This systematic review and meta-analysis indicates that differences exist between adjunctive atypical antipsychotics in the treatment of MDD with respect to overall efficacy and acceptability, which should be simultaneously considered. The absence of adequate and well-controlled studies documenting maintenance efficacy of adjunctive atypical antipsychotics in MDD remains a knowledge gap.32:Tfed, Importance Most adults living with major depressive disorder (MDD) fail to achieve remission with conventional antidepressants. The US Food and Drug Administration (FDA) has approved 5 atypical antipsychotics in MDD on the basis of their substantial evidence of efficacy and safety. Objective To compare the efficacy and acceptability of FDA-approved atypical antipsychotics for the adjunctive treatment of MDD in order to provide decision support to practitioners and persons with lived experience. Data Sources A systematic search was conducted using PubMed/MEDLINE, PsycINFO, the Cochrane Library, and Embase from database inception through July 15, 2025. Study Selection Six independent raters screened publications for eligibility. Inclusion criteria were atypical antipsychotics that are FDA approved in the adjunctive treatment of MDD. Data Extraction and Synthesis Two independent raters obtained data and examined risk of bias in accordance with the Cochrane criteria. Effect sizes were synthesized using random-effects models. Data were analyzed from August to September 2025. Main Outcomes and Measures The primary outcomes were efficacy (ie, ≥50% reduction from baseline in the total Montgomery-Åsberg Depression Rating Scale [MADRS] score) and acceptability (ie, all-cause discontinuation). Results A total of 22 short-term studies comprising 10 962 participants (aripiprazole: n = 1297; brexpiprazole: n = 1973; cariprazine: n = 1894; lumateperone: n = 483; quetiapine extended release [XR]: n = 719; and placebo: n = 4596) were included for analysis. Lumateperone had the highest effect size for efficacy (risk ratio [RR], 1.72; 95% credible interval [CrI], 1.40-2.15), followed by aripiprazole (RR, 1.53; 95% CrI, 1.32-1.77), brexpiprazole (RR, 1.38; 95% CrI, 1.18-1.65), cariprazine (RR, 1.20; 95% CrI, 1.07-1.36), and quetiapine XR (RR, 1.15; 95% CrI, 0.96-1.35). A hierarchy of acceptability was observed, with aripiprazole exhibiting the highest acceptability (RR, 1.16; 95% CrI, 0.89-1.50), followed by cariprazine (RR, 1.44; 95% CrI, 1.15-1.82), brexpiprazole (RR, 1.47; 95% CrI, 1.18-1.85), quetiapine XR (RR, 1.56; 95% CrI, 1.14-2.12), and lumateperone (RR, 2.30; 95% CrI, 1.45-3.84). Secondary outcomes (eg, symptomatic remission) and exploratory outcomes (eg, clinically significant weight gain) accorded with the coprimary outcomes. Conclusions and Relevance This systematic review and meta-analysis indicates that differences exist between adjunctive atypical antipsychotics in the treatment of MDD with respect to overall efficacy and acceptability, which should be simultaneously considered. The absence of adequate and well-controlled studies documenting maintenance efficacy of adjunctive atypical antipsychotics in MDD remains a knowledge gap. 33:T907,Hand-foot syndrome (HFS) is a common dose-limiting toxic effect of several chemotherapy agents, particularly capecitabine. Despite its substantial impact on the patient's quality of life and potential to compromise therapeutic efficacy, effective preventive strategies remain limited. To evaluate and compare the efficacy of pharmacologic interventions for the prevention of chemotherapy-induced HFS through a network meta-analysis of published results of randomized clinical trials (RCTs). PubMed, Embase, and Cochrane CENTRAL were systematically searched from inception through November 2024 for relevant RCTs. Eligible studies were phase 2 or 3 RCTs that compared systemic or topical prophylactic interventions for the prevention of HFS. Data extraction was performed by 2 reviewers, and disagreements were resolved by consensus. Risk of bias was assessed using the Cochrane Risk of Bias tool. A frequentist random-effects network meta-analysis was conducted. The primary income was incidence of grade 2 or higher HFS. The secondary outcome was the incidence of any-grade HFS. Odds ratios (ORs) with 95% CIs were estimated. Ranking was assessed using P-scores and surface under the cumulative ranking (SUCRA) values. Nineteen RCTs were included, of which 17 trials comprising 2192 patients (median [range] age, 57 [56-61] years) were analyzed for the primary outcome. Compared with placebo, topical silymarin (OR, 0.08; 95% CI, 0.01-0.71), diclofenac (OR, 0.23; 95% CI, 0.08-0.62), 400-mg pyridoxine (OR, 0.28; 95% CI, 0.09-0.88), and celecoxib (OR, 0.41; 95% CI, 0.18-0.95) significantly reduced grade 2 or higher HFS. Diclofenac (OR, 0.30; 95% CI, 0.13-0.69) and celecoxib (OR, 0.46; 95% CI, 0.22-0.94) also reduced overall HFS incidence. In contrast, silymarin and 400-mg pyridoxine did not show benefit for overall HFS, while mapisal increased HFS risk (OR, 3.04; 95% CI, 1.07-8.64). Ranking analyses showed the highest SUCRA value for silymarin (0.91) and diclofenac (0.76). In this systematic review and network meta-analysis, diclofenac and silymarin were the most effective preventive strategies for HFS, with silymarin requiring confirmation in a larger randomized trial. Diclofenac emerged as the agent with the best overall supporting evidence, informed by both effect estimates and study quality.34:Te8e, Importance Hand-foot syndrome (HFS) is a common dose-limiting toxic effect of several chemotherapy agents, particularly capecitabine. Despite its substantial impact on the patient’s quality of life and potential to compromise therapeutic efficacy, effective preventive strategies remain limited. Objective To evaluate and compare the efficacy of pharmacologic interventions for the prevention of chemotherapy-induced HFS through a network meta-analysis of published results of randomized clinical trials (RCTs). Data Sources PubMed, Embase, and Cochrane CENTRAL were systematically searched from inception through November 2024 for relevant RCTs. Study Selection Eligible studies were phase 2 or 3 RCTs that compared systemic or topical prophylactic interventions for the prevention of HFS. Data Extraction and Synthesis Data extraction was performed by 2 reviewers, and disagreements were resolved by consensus. Risk of bias was assessed using the Cochrane Risk of Bias tool. A frequentist random-effects network meta-analysis was conducted. Main Outcomes and Measures The primary income was incidence of grade 2 or higher HFS. The secondary outcome was the incidence of any-grade HFS. Odds ratios (ORs) with 95% CIs were estimated. Ranking was assessed using P-scores and surface under the cumulative ranking (SUCRA) values. Results Nineteen RCTs were included, of which 17 trials comprising 2192 patients (median [range] age, 57 [56-61] years) were analyzed for the primary outcome. Compared with placebo, topical silymarin (OR, 0.08; 95% CI, 0.01-0.71), diclofenac (OR, 0.23; 95% CI, 0.08-0.62), 400-mg pyridoxine (OR, 0.28; 95% CI, 0.09-0.88), and celecoxib (OR, 0.41; 95% CI, 0.18-0.95) significantly reduced grade 2 or higher HFS. Diclofenac (OR, 0.30; 95% CI, 0.13-0.69) and celecoxib (OR, 0.46; 95% CI, 0.22-0.94) also reduced overall HFS incidence. In contrast, silymarin and 400-mg pyridoxine did not show benefit for overall HFS, while mapisal increased HFS risk (OR, 3.04; 95% CI, 1.07-8.64). Ranking analyses showed the highest SUCRA value for silymarin (0.91) and diclofenac (0.76). Conclusions and Relevance In this systematic review and network meta-analysis, diclofenac and silymarin were the most effective preventive strategies for HFS, with silymarin requiring confirmation in a larger randomized trial. Diclofenac emerged as the agent with the best overall supporting evidence, informed by both effect estimates and study quality. 35:T818,Non-cystic fibrosis bronchiectasis (NCFB) is characterized by chronic respiratory symptoms and radiologic airway dilatation. Sustained neutrophilic inflammation is a key driver, prompting interest in anti-inflammatory pharmacotherapy as a new treatment paradigm; however, comparisons among anti-inflammatory agents are lacking. What is the current profile concerning efficacy and safety of anti-inflammatory therapies for bronchiectasis? We performed a systematic review and network meta-analysis (NMA) of randomized controlled trials that evaluated inhaled or oral anti-inflammatory agents in adults with CT-confirmed bronchiectasis. PubMed, Embase, CENTRAL, Web of Science, ICTRP, and ClinicalTrials.gov were searched. Trials enrolling adults and employing ≥4 weeks of treatment were eligible. The primary outcome was the rate of overall and severe exacerbations; secondary outcomes were quality of life, 6-min walk distance, FEV Thirty-one trials (n = 4,092) evaluating eight anti-inflammatory agents were included. Compared with placebo, macrolides (rate ratio [RR] 0.44, 95 % confidence interval [CI] 0.35-0.56) and DPP-1 inhibitors (RR 0.73, 95% CI 0.60-0.88) reduced overall exacerbation frequency (both moderate certainty). DPP-1 inhibitors reduced the frequency of severe exacerbations (RR 0.70, 95% CI 0.54-0.89; moderate certainty). Macrolides showed a similar downward trend of severe exacerbations with very serious imprecision (RR 0.54, 95 % CI 0.19-1.54; low certainty). Adverse events and treatment discontinuation rates were trivial or small for all interventions. In subgroup analyses, DPP-1 inhibitors remained effective irrespective of baseline long-term macrolide use (with macrolide: RR 0.77, 95% CI 0.60-0.99; without macrolide: RR 0.77, 95% CI 0.67-0.89). Among individual macrolides, azithromycin showed the greatest reduction in exacerbation frequency (RR 0.37, 95% CI 0.29-0.48). These findings support the use of DPP-1 inhibitors and macrolide antibiotics as anti-inflammatory treatment options for bronchiectasis with frequent exacerbations.36:T89f,Janus kinase inhibitors (JAKis) have revolutionized the management of moderate-to-severe atopic dermatitis (AD). Although agents approved by the United States Food and Drug Administration (FDA), such as upadacitinib and abrocitinib, are widely used, and baricitinib and ivarmacitinib are under investigation, direct head-to-head randomized clinical trials (RCTs) comparing these agents are lacking. Our aim was to rank the short-term efficacy of four oral JAKis, upadacitinib (15/30 mg), abrocitinib (100/200 mg), baricitinib (2/4 mg), and ivarmacitinib (4/8 mg), in moderate-to-severe AD using a Bayesian Network Meta-Analysis (BNMA). Conducted per PRISMA 2020 guidelines and registered in PROSPERO (CRD420251116775), this study systematically reviewed phase 2 and 3 RCTs evaluating JAKi monotherapy in adults with moderate-to-severe AD. Primary endpoints included: (1) ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), (2) Investigator's Global Assessment (IGA-AD 0/1), and (3) ≥ 4-point reduction in itch numeric rating scale (Itch NRS) at 12-16 weeks. Bayesian hierarchical modeling estimated odds ratios (ORs) with 95% credible intervals (CrIs), and surface under the cumulative ranking curve (SUCRA) probabilities defined the treatment hierarchy. Nine RCTs (n = 4261) were included. Upadacitinib 30 mg demonstrated the greatest efficacy across all endpoints, EASI-75 (OR = 12.3; 95% CrI 7.9-18.7), IGA-AD 0/1 (OR = 18.9; 95% CrI 12.0-29.7), and Itch NRS (OR = 11.1; 95% CrI 7.2-17.5), followed by upadacitinib 15 mg, abrocitinib 200 mg, and ivarmacitinib 8 mg. Baricitinib 2 mg and 4 mg consistently ranked lowest. SUCRA values confirmed upadacitinib 30 mg as the top performer (97%-98%). Among oral JAKis, upadacitinib 30 mg, followed by upadacitinib 15 mg, achieved the most consistent short-term efficacy, providing superior skin clearance and itch relief. Abrocitinib 200 mg and ivarmacitinib 8 mg showed intermediate benefits, whereas baricitinib displayed modest effects. These findings support a provisional efficacy preference for upadacitinib in managing moderate-to-severe AD unresponsive to biologic or topical therapies.37:Td01,ABSTRACT Background Janus kinase inhibitors (JAKis) have revolutionized the management of moderate‐to‐severe atopic dermatitis (AD). Although agents approved by the United States Food and Drug Administration (FDA), such as upadacitinib and abrocitinib, are widely used, and baricitinib and ivarmacitinib are under investigation, direct head‐to‐head randomized clinical trials (RCTs) comparing these agents are lacking. Objective Our aim was to rank the short‐term efficacy of four oral JAKis, upadacitinib (15/30 mg), abrocitinib (100/200 mg), baricitinib (2/4 mg), and ivarmacitinib (4/8 mg), in moderate‐to‐severe AD using a Bayesian Network Meta‐Analysis (BNMA). Methods Conducted per PRISMA 2020 guidelines and registered in PROSPERO (CRD420251116775), this study systematically reviewed phase 2 and 3 RCTs evaluating JAKi monotherapy in adults with moderate‐to‐severe AD. Primary endpoints included: (1) ≥ 75% improvement in Eczema Area and Severity Index (EASI‐75), (2) Investigator's Global Assessment (IGA‐ AD 0/1), and (3) ≥ 4‐point reduction in itch numeric rating scale (Itch NRS) at 12–16 weeks. Bayesian hierarchical modeling estimated odds ratios (ORs) with 95% credible intervals (CrIs), and surface under the cumulative ranking curve (SUCRA) probabilities defined the treatment hierarchy. Results Nine RCTs ( n = 4261) were included. Upadacitinib 30 mg demonstrated the greatest efficacy across all endpoints, EASI‐75 (OR = 12.3; 95% CrI 7.9–18.7), IGA‐ AD 0/1 (OR = 18.9; 95% CrI 12.0–29.7), and Itch NRS (OR = 11.1; 95% CrI 7.2–17.5), followed by upadacitinib 15 mg, abrocitinib 200 mg, and ivarmacitinib 8 mg. Baricitinib 2 mg and 4 mg consistently ranked lowest. SUCRA values confirmed upadacitinib 30 mg as the top performer (97%–98%). Conclusion Among oral JAKis, upadacitinib 30 mg, followed by upadacitinib 15 mg, achieved the most consistent short‐term efficacy, providing superior skin clearance and itch relief. Abrocitinib 200 mg and ivarmacitinib 8 mg showed intermediate benefits, whereas baricitinib displayed modest effects. These findings support a provisional efficacy preference for upadacitinib in managing moderate‐to‐severe AD unresponsive to biologic or topical therapies. 38:T800,Improving population well-being is increasingly recognized as a global priority, yet evidence on the comparative effectiveness of well-being-focused interventions in adults is fragmented. Here we conduct a preregistered systematic review and network meta-analysis (PROSPERO CRD42023403480) of randomized controlled trials evaluating well-being interventions in adults without diagnosed conditions. Searches of MEDLINE, PsycINFO, CENTRAL and Scopus (to March 2023) identified 183 trials (n = 22,811). Interventions included mindfulness-based, compassion-based, acceptance and commitment therapy and positive psychology interventions, as well as exercise, yoga, educational, nature-based programmes and combined exercise-psychological approaches. Risk of bias was assessed using RoB 2, and data were synthesized using random-effects network meta-analysis. Most interventions improved well-being compared with inactive controls. Combined exercise-psychological interventions produced the largest effect (standardized mean difference of 0.73, 95% confidence interval 0.27 to 1.20). Mindfulness, compassion, single positive psychology, yoga and exercise interventions demonstrated moderate, consistent effects (standardized mean difference of 0.41-0.49), with no significant differences between interventions. Nature-based interventions were not significantly more effective than controls, but evidence was limited by conceptual and methodological heterogeneity. Risk of bias was frequently moderate to high, and funnel plot asymmetry suggested potential publication bias. However, multiple sensitivity analyses (including grey literature, excluding studies with high risk of bias and small studies) supported the robustness of overall conclusions. Most comparisons (71%) were rated as moderate in certainty of evidence using CINEMA. These findings provide an integrated synthesis of the well-being intervention literature and highlight priority areas for future interdisciplinary, methodologically robust research. No external funding was received.39:T8b4,Abstract Improving population well-being is increasingly recognized as a global priority, yet evidence on the comparative effectiveness of well-being-focused interventions in adults is fragmented. Here we conduct a preregistered systematic review and network meta-analysis (PROSPERO CRD42023403480) of randomized controlled trials evaluating well-being interventions in adults without diagnosed conditions. Searches of MEDLINE, PsycINFO, CENTRAL and Scopus (to March 2023) identified 183 trials ( n = 22,811). Interventions included mindfulness-based, compassion-based, acceptance and commitment therapy and positive psychology interventions, as well as exercise, yoga, educational, nature-based programmes and combined exercise-psychological approaches. Risk of bias was assessed using RoB 2, and data were synthesized using random-effects network meta-analysis. Most interventions improved well-being compared with inactive controls. Combined exercise-psychological interventions produced the largest effect (standardized mean difference of 0.73, 95% confidence interval 0.27 to 1.20). Mindfulness, compassion, single positive psychology, yoga and exercise interventions demonstrated moderate, consistent effects (standardized mean difference of 0.41–0.49), with no significant differences between interventions. Nature-based interventions were not significantly more effective than controls, but evidence was limited by conceptual and methodological heterogeneity. Risk of bias was frequently moderate to high, and funnel plot asymmetry suggested potential publication bias. However, multiple sensitivity analyses (including grey literature, excluding studies with high risk of bias and small studies) supported the robustness of overall conclusions. Most comparisons (71%) were rated as moderate in certainty of evidence using CINEMA. These findings provide an integrated synthesis of the well-being intervention literature and highlight priority areas for future interdisciplinary, methodologically robust research. No external funding was received. 3a:T710,Many biologic therapies are available for moderate-to-severe plaque psoriasis. A systematic literature review and network meta-analysis (NMA) was conducted to compare the efficacy of the interleukin (IL)-23 inhibitor, tildrakizumab, with other biologics at up to 28 weeks of treatment. The literature search was conducted on January 22, 2024, searching MEDLINE, Embase, and CENTRAL for randomized controlled trials (RCTs) investigating the comparative efficacy and safety of biologics in adult Asian patients with moderate-to-severe plaque psoriasis. NMAs were conducted for ≥ 75%, ≥ 90%, and 100% reduction in Psoriasis Area and Severity Index score (PASI 75, 90, and 100) and achieving a Physician Global Assessment (PGA) score of 0 or 1 after the induction period (12 and 16 weeks) and mid-term (28 weeks) follow-up. NMAs were conducted using the Bayesian framework outlined in the National Institute of Clinical Excellence guidelines. Nineteen RCTs conducted in China, Japan, Korea, and Taiwan with 11 different biologics were included. At Week 12, tildrakizumab had lower efficacy compared to other biologics. Between Weeks 12 and 28, the proportion of patients achieving PASI 75/90/100 with tildrakizumab increased from 60.77% to 81.84%, from 38.54% to 71.23%, and from 6.97% to 22.64%, respectively. At Week 28, tildrakizumab efficacy was comparable to other biologic therapies studied here, including tumor necrosis factor-alpha (TNFα), IL-17, IL-12/IL-23, and other IL-23 inhibitors. The efficacy of tildrakizumab improved over time, which underscores the importance of evaluating the sustained efficacy of tildrakizumab over the long term. Combined with low dosing frequency, tildrakizumab offers an effective treatment option for patients with moderate-to-severe plaque psoriasis.3b:T760,ABSTRACTMany biologic therapies are available for moderate‐to‐severe plaque psoriasis. A systematic literature review and network meta‐analysis (NMA) was conducted to compare the efficacy of the interleukin (IL)‐23 inhibitor, tildrakizumab, with other biologics at up to 28 weeks of treatment. The literature search was conducted on January 22, 2024, searching MEDLINE, Embase, and CENTRAL for randomized controlled trials (RCTs) investigating the comparative efficacy and safety of biologics in adult Asian patients with moderate‐to‐severe plaque psoriasis. NMAs were conducted for ≥ 75%, ≥ 90%, and 100% reduction in Psoriasis Area and Severity Index score (PASI 75, 90, and 100) and achieving a Physician Global Assessment (PGA) score of 0 or 1 after the induction period (12 and 16 weeks) and mid‐term (28 weeks) follow‐up. NMAs were conducted using the Bayesian framework outlined in the National Institute of Clinical Excellence guidelines. Nineteen RCTs conducted in China, Japan, Korea, and Taiwan with 11 different biologics were included. At Week 12, tildrakizumab had lower efficacy compared to other biologics. Between Weeks 12 and 28, the proportion of patients achieving PASI 75/90/100 with tildrakizumab increased from 60.77% to 81.84%, from 38.54% to 71.23%, and from 6.97% to 22.64%, respectively. At Week 28, tildrakizumab efficacy was comparable to other biologic therapies studied here, including tumor necrosis factor‐alpha (TNFα), IL‐17, IL‐12/IL‐23, and other IL‐23 inhibitors. The efficacy of tildrakizumab improved over time, which underscores the importance of evaluating the sustained efficacy of tildrakizumab over the long term. Combined with low dosing frequency, tildrakizumab offers an effective treatment option for patients with moderate‐to‐severe plaque psoriasis.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Systematic Review and Network Meta-Analysis: study design Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Systematic Review and Network Meta-Analysis (study design). Clinician-written summaries and actionable practice insights. 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pooling across brands was not performed but both appear in the analysis.","value_numeric":null},{"paper_doi":"10.1038/s41380-026-03759-1","tag_type":"warning","value":"The network includes 137 distinct compound combinations across 163 trials, making many node comparisons sparse and indirect; transitivity assumptions may not fully hold.","value_numeric":null}],"summaries":{"what_studied":"A systematic review and network meta-analysis of 163 RCTs (n = 15,757) evaluated nutraceuticals and phytoceuticals vs. placebo or antidepressants (TAU) for major depressive disorder (MDD), examining depressive symptoms, treatment response, remission, anxiety, tolerability, and acceptability.","key_result":"After restricting to high-quality evidence (≥2 RCTs, low risk of bias, non-sponsored, non-outlier), EPA (SMD = −1.67), vitamin D3 (SMD = −1.59), and St. John's wort extract ZE117 (SMD = −1.02) showed the largest effect sizes vs. placebo for depressive symptoms — but these effect sizes were deemed higher-than-expected or unrealistic. Curcumin showed a moderate benefit for anxiety (SMD = −0.58). Citicoline was linked to significantly more dropouts. Overall confidence in evidence was **low to very low**, and larger effect sizes correlated with lower study quality (meta-regression).","limitations":"- Substantial heterogeneity (I² = 85.3%) and significant global inconsistency limit pooled estimates.\n- Confidence in all evidence rated low to very low (CINeMA/AMSTAR-Plus).\n- Even filtered analyses produced effect sizes judged unrealistically large, suggesting residual bias.","practice_takeaway":"Clinicians should be cautious about recommending nutraceuticals or phytoceuticals for MDD — current evidence is low quality, and apparent large benefits (especially for EPA, vitamin D3, and St. John's wort) are likely inflated by poor study design. Rigorous, well-powered RCTs are needed before routine use can be supported."}},{"doi":"10.1136/bmj-2026-100163","pmid":"42526949","title":"Antihistamines for atopic dermatitis (eczema): systematic review and network meta-analysis of randomised trials","journal_title":"BMJ","journal_issn":"1756-1833","published_at":"2026-07-29T00:00:00.000Z","url":"https://doi.org/10.1136/bmj-2026-100163","source_score":136,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:18:04.441Z","updated_at":"2026-08-04T18:18:04.441Z","tags":[{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"condition","value":"Atopic Dermatitis","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"generic","value":"cetirizine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"generic","value":"levocetirizine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"generic","value":"loratadine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"generic","value":"nedocromil sodium","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"generic","value":"sodium cromoglycate","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"modality","value":"Antihistamine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"modality","value":"H1 Antihistamine","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"modality","value":"H2 Blocker","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"modality","value":"Mast Cell Stabiliser","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"sample_size","value":"n=6230","value_numeric":6230},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"warning","value":"H2 blockers and mast cell stabilisers are included in the study design but specific effect estimates for these agents are not reported in the abstract; summaries are limited to what is explicitly stated.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"warning","value":"Network meta-analysis includes indirect comparisons; certainty ratings vary by outcome (moderate for severity/itch/cognitive harms, low for sleep/exacerbations).","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-100163","tag_type":"warning","value":"The paper's DOI includes the year 2026 in its identifier (bmj-2026-100163), consistent with the stated publication date of July 29, 2026; this is unusual but taken at face value.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and network meta-analysis evaluated add-on oral H1 antihistamines (first- and second-generation), H2 blockers, and mast cell stabilisers vs. placebo in 47 RCTs enrolling 6,230 children and adults with primarily moderate-to-severe atopic dermatitis, searching databases through May 2025.","key_result":"Adding H1 antihistamines yielded only small, clinically unimportant reductions in disease severity (MD −1.87 on oSCORAD, MID 8.2) and itch (MD −0.89 on NRS 0–10, MID 3.0; moderate certainty). Sleep disturbance and exacerbations were not improved (low certainty). First-generation agents increased cognitive impairment and treatment discontinuation (RD +66 per 1,000; moderate certainty); among second-generation agents, loratadine showed 0 excess cognitive events vs. 16–17 more per 1,000 for levocetirizine and cetirizine.","limitations":"- Low certainty evidence for sleep and exacerbation outcomes limits conclusions for those endpoints.\n- Enrolled populations had primarily moderate-to-severe disease, so findings may not generalise to mild atopic dermatitis.\n- Network meta-analysis relies on indirect comparisons across heterogeneous trials, which may affect precision.","practice_takeaway":"Routine oral antihistamine use for atopic dermatitis is not supported by evidence — any benefit falls well below what patients notice, while first-generation agents carry meaningful cognitive risks. If an antihistamine must be used, loratadine appears to carry the lowest cognitive impairment risk among second-generation options."}},{"doi":"10.14218/jcth.2025.00596","pmid":null,"title":"Comparative Efficacy of Promising Targets in the Treatment of Metabolic Dysfunction-associated Steatotic Liver Disease and Steatohepatitis: A Systematic Review and Network Meta-analysis","journal_title":"Journal of Clinical and Translational Hepatology","journal_issn":"2225-0719","published_at":"2026-07-20T00:00:00.000Z","url":"https://doi.org/10.14218/jcth.2025.00596","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-07-26T13:44:53.172Z","updated_at":"2026-07-26T13:44:53.172Z","tags":[{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"brand","value":"Rezdiffra","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"brand","value":"Wegovy","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatohepatitis","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"condition","value":"Metabolic Dysfunction-Associated Steatotic Liver Disease","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"efruxifermin","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"lanifibranor","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"liraglutide","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"pegozafermin","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"pioglitazone","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"resmetirom","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"retatrutide","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"generic","value":"tirzepatide","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"ACC Inhibitor","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"FGF21 Analog","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"FXR Agonist","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"GLP-1/GCG Dual Receptor Agonist","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"GLP-1/GIP Dual Receptor Agonist","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"GLP-1/GIP/GCG Triple Receptor Agonist","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"PPAR Agonist","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"modality","value":"Thyroid Hormone Receptor-Beta Agonist","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"sample_size","value":"n=11410","value_numeric":11410},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"warning","value":"d-(R)-pioglitazone's high SUCRA ranking for fibrosis improvement is based on a single small-biopsy-subset trial (DESTINY-1); CINeMA certainty was very low — this ranking should not be used to drive prescribing.","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"warning","value":"Resmetirom and semaglutide received FDA approval for MASH (F2–F3) after the search cutoff or near it; their SUCRA rankings in this NMA do not reflect their full phase 3 evidence base and should not be interpreted as evidence of inferiority.","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"warning","value":"The impact_flag 'practice_changing' was applied cautiously: while the NMA synthesizes the most current evidence across 11 targets, most active-vs-active comparisons rely on indirect evidence with low-to-very-low CINeMA certainty, and no new therapies received regulatory approval within this paper itself.","value_numeric":null},{"paper_doi":"10.14218/jcth.2025.00596","tag_type":"warning","value":"The paper is dated July 2026, which is beyond the current knowledge cutoff for standard AI training data; content has been extracted solely from the provided full text.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and network meta-analysis compared 11 pharmacologic targets (33 medications) across 44 RCTs (n=11,410 adults) for MASLD/MASH, evaluating fibrosis improvement ≥1 stage without steatohepatitis worsening, steatohepatitis resolution without fibrosis worsening, liver fat content, liver enzymes, metabolic profiles, non-invasive tests, and safety outcomes (search through November 20, 2024).","key_result":"For fibrosis improvement, d-(R)-pioglitazone (OR 4.75, SUCRA 79.3) and FGF21 analogs (OR 3.52, SUCRA 71.9) ranked highest. For steatohepatitis resolution, GLP-1/GIP dual receptor agonists ranked highest (OR 14.33, SUCRA 91.7), followed by GLP-1/GCG dual agonists (OR 10.67). GLP-1/GIP/GCG triple agonists ranked best for relative LFC reduction (mean difference −81.40%). GLP-1 RA and GLP-1/GCG dual RA had significantly higher rates of any AEs vs. placebo; FXR agonists and GLP-1/GCG dual RA had higher discontinuation rates; no target significantly increased SAEs or cardiovascular events.","limitations":"- Most histological evidence came from single trials with small biopsy subsets (especially d-(R)-pioglitazone, based on one 36-week trial), making SUCRA rankings unstable and CINeMA certainty low or very low for most comparisons.\n- Predominantly placebo-centered network with no direct head-to-head comparisons; active-versus-active estimates derived largely from indirect evidence, limiting reliability.\n- Trials excluded cirrhotic (F4) patients and varied widely in duration (16–72 weeks), baseline fibrosis stage, BMI, and metabolic comorbidities, constraining generalizability and transitivity.","practice_takeaway":"Incretin-based co-agonists (particularly GLP-1/GIP dual agonists like tirzepatide) and FGF21 analogs show the most promising signals across liver histology and metabolic endpoints, but certainty of evidence is low to very low and no head-to-head trials exist — treatment choice should still incorporate fibrosis stage, comorbidities, and tolerability. Both FDA-approved agents (resmetirom for F2–F3 MASH, semaglutide for F2–F3 MASH) remain established first-line options supported by larger phase 3 data."}},{"doi":"10.1016/j.ard.2026.06.017","pmid":"42431784","title":"Cancer risk of Janus kinase inhibitors and other advanced therapies in immune-mediated inflammatory diseases: a systematic review and Bayesian network meta-analysis of RCTs","journal_title":"Annals of the Rheumatic Diseases","journal_issn":"0003-4967","published_at":"2026-07-10T00:00:00.000Z","url":"https://doi.org/10.1016/j.ard.2026.06.017","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-23T13:33:19.238Z","updated_at":"2026-07-23T13:33:19.238Z","tags":[{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"condition","value":"Inflammatory Bowel Disease","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"condition","value":"Psoriasis","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"condition","value":"Psoriatic Arthritis","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"condition","value":"Rheumatoid Arthritis","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"generic","value":"tofacitinib","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"CD20 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"CTLA-4 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"IL-12/23 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"IL-17 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"IL-23 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"IL-6 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"modality","value":"TNF Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"sample_size","value":"n=164824","value_numeric":164824},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"warning","value":"Class-level pooling of JAK inhibitors may mask agent-specific or dose-specific differences; individual drug comparisons are not reported.","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"warning","value":"Long-term extension studies are included alongside RCTs, which may introduce exposure-time bias favoring detection of malignancy in longer studies.","value_numeric":null},{"paper_doi":"10.1016/j.ard.2026.06.017","tag_type":"warning","value":"The absolute risk calculations depend on assumed baseline cancer incidence rates for 'standard-risk' vs 'higher-risk' populations, which are not fully specified in the abstract—clinicians should interpret absolute numbers cautiously without the full paper.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and Bayesian network meta-analysis evaluated relative and absolute cancer risk of JAK inhibitors (JAKis) vs other advanced therapies (TNFi, IL-6, IL-17, IL-23, IL-12/23, CTLA-4, CD20 inhibitors) across immune-mediated inflammatory diseases (RA, PsO/PsA, IBD) using 305 RCTs and long-term extension studies (164,824 participants; 264,100 person-years exposure) published up to February 2026.","key_result":"JAKis were associated with higher malignancy risk than TNFi (RR 1.60; 95% CrI 1.27–2.02) and standard care (RR 1.85; 95% CrI 1.38–2.47) across all three disease areas. Absolute excess risk vs TNFi was negligible in standard-risk patients (~1 extra cancer per 27,000 person-years) but clinically meaningful in high-risk patients (~1 extra cancer per 147 person-years). IL-6, IL-17, IL-23, IL-12/23, CTLA-4, and CD20 inhibitors showed cancer risks broadly comparable to TNFi.","limitations":"- Relies on RCT and long-term extension data, which may underrepresent older or higher-risk patients seen in routine care.\n- Class-level pooling may obscure differences between individual JAKi agents or doses.\n- Malignancy outcomes (including non-melanoma skin cancer) vary in ascertainment and reporting across trials.","practice_takeaway":"Clinicians should apply risk-stratified decision-making when prescribing JAKis across all IMIDs—not just RA—particularly in patients with prior malignancy or other cancer risk factors. For standard-risk patients the absolute excess risk vs TNFi is very small, but it becomes meaningful in higher-risk populations (~1 extra cancer per 147 person-years)."}},{"doi":"10.1136/bmj-2026-372161","pmid":"42419792","title":"Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis","journal_title":"BMJ","journal_issn":"1756-1833","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1136/bmj-2026-372161","source_score":150,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-12T13:19:47.107Z","updated_at":"2026-07-12T13:19:47.107Z","tags":[{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"brand","value":"Contrave","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"brand","value":"Mounjaro","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"brand","value":"Qsymia","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"brand","value":"Rybelsus","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"brand","value":"Wegovy","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"category","value":"Medicine, General & Internal","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"condition","value":"Overweight","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"cagrilintide-semaglutide","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"ecnoglutide","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"liraglutide","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"mazdutide","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"naltrexone-bupropion","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"orforglipron","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"phentermine-topiramate","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"retatrutide","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"generic","value":"tirzepatide","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"modality","value":"Amylin/GLP-1 Combination","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"modality","value":"GIP/GLP-1 Dual Agonist","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"modality","value":"Opioid Antagonist/Dopamine-Norepinephrine Reuptake Inhibitor Combination","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"modality","value":"Sympathomimetic/Anticonvulsant Combination","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"sample_size","value":"n=99791","value_numeric":99791},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"warning","value":"Brand name tags are inferred from generic names and common market approvals; the paper itself does not list brand names.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"warning","value":"CagriSema (cagrilintide-semaglutide) is an investigational combination agent; it is not yet widely approved, and certainty of evidence is moderate.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"warning","value":"Cardiovascular outcome benefits (mortality, MI) for subcutaneous semaglutide are largely derived from high-risk cardiovascular trial populations and may not apply to the general obesity population.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"warning","value":"Orforglipron is an oral non-peptide GLP-1 receptor agonist still in late-stage development; its approval status varies by region.","value_numeric":null},{"paper_doi":"10.1136/bmj-2026-372161","tag_type":"warning","value":"The paper's DOI references a 2026 publication date, which is after the current knowledge cutoff for some readers; results include several emerging agents not yet in standard clinical practice.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and network meta-analysis compared 19 drugs for overweight/obesity across 24 outcomes in 262 RCTs (99,791 adults, follow-up 12–172 weeks), using frequentist random effects and Bayesian dose-response models with GRADE certainty ratings.","key_result":"At one year, tirzepatide led weight loss vs. lifestyle modification alone (−14.9%), followed by CagriSema (−14.8%), oral semaglutide (−10.9%), orforglipron (−9.9%), subcutaneous semaglutide (−9.8%), and phentermine-topiramate (−8.1%). Only subcutaneous semaglutide reduced all-cause mortality (RR 0.81, 95% CI 0.72–0.93) and MI (RR 0.72, 0.61–0.85); semaglutide and tirzepatide both reduced heart failure risk. No drug improved quality of life beyond the minimally important difference (10 points; all mean differences <5). Discontinuation due to adverse events was highest with orforglipron (RR 4.2) and fatigue was most marked with naltrexone-bupropion (RR 8.9; +331 per 1,000/year).","limitations":"- Cardiovascular mortality and MI benefits for subcutaneous semaglutide are largely driven by trials in high-risk cardiovascular populations, limiting generalizability to lower-risk groups.\n- Quality-of-life data came from only 43 of 262 trials, potentially underrepresenting important patient-centered outcomes.\n- Emerging agents (ecnoglutide, mazdutide, retatrutide) carry very low to low certainty evidence, restricting firm conclusions.","practice_takeaway":"When choosing an obesity drug, weigh the degree of weight loss against the tolerability profile: tirzepatide and CagriSema offer the greatest weight reduction but carry significant GI and fatigue burdens, while subcutaneous semaglutide is currently the only agent with demonstrated mortality and MI reduction. Shared decision-making should explicitly address trade-offs, as no drug meaningfully improves quality of life beyond placebo."}},{"doi":"10.1001/jamapsychiatry.2026.1814","pmid":"42418179","title":"Pharmacological Interventions for Weight Reduction in Patients With Schizophrenia Treated With Antipsychotics","journal_title":"JAMA Psychiatry","journal_issn":"2168-622X","published_at":"2026-07-08T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13347271/","source_score":16,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:02.454Z","updated_at":"2026-07-14T13:24:02.454Z","tags":[{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"brand","value":"Byetta","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"brand","value":"Glucophage","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"brand","value":"Topamax","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"brand","value":"Victoza","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"category","value":"Psychiatry","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"condition","value":"Antipsychotic-Induced Weight Gain","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"condition","value":"Schizophrenia Spectrum Disorder","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"generic","value":"exenatide","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"generic","value":"liraglutide","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"generic","value":"metformin","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"generic","value":"topiramate","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"modality","value":"Antiepileptic","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"modality","value":"Biguanide","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"sample_size","value":"n=5898","value_numeric":5898},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"warning","value":"Brand name tags for generic drugs are provided for common formulations but may not reflect the specific products used across the 95 included trials.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"warning","value":"Full text is under PMC embargo until July 2027; all extracted data are based solely on the published abstract. Methodological details such as individual study durations, risk of bias assessments, and subgroup analyses could not be verified.","value_numeric":null},{"paper_doi":"10.1001/jamapsychiatry.2026.1814","tag_type":"warning","value":"The 'mixed sex' tag is inferred from the population type and study scope; sex breakdown is not explicitly reported in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and frequentist random-effects network meta-analysis evaluated 39 pharmacological interventions for antipsychotic-induced weight gain in adults with schizophrenia spectrum disorders (SSDs), drawing from 95 RCTs (pooled N = 5,898) identified through searches up to December 2025.","key_result":"Semaglutide produced the largest weight reduction vs. placebo (MD −10.98 kg; 95% CI −13.33 to −8.62; moderate certainty), followed by liraglutide (−5.43 kg), topiramate (−3.95 kg), metformin (−3.86 kg), and exenatide (−2.97 kg). Clinically meaningful weight loss (≥5%) was observed only with semaglutide and metformin. No major safety signals for GI adverse effects or dropout rates were identified across interventions.","limitations":"- Full text was under embargo; results are drawn from the abstract only, limiting appraisal of methodological detail.\n- Individual trial durations varied, and no restriction on study length was applied, which may introduce heterogeneity.\n- Several interventions (e.g., ramelteon, nizatidine, aripiprazole) had very low certainty evidence, limiting confidence in their effect estimates.","practice_takeaway":"For patients with schizophrenia on antipsychotics who have gained significant weight, semaglutide or metformin offer the strongest evidence for clinically meaningful weight loss (≥5%) and should be considered first-line pharmacological options. Liraglutide, topiramate, and exenatide are reasonable alternatives with moderate-certainty evidence."}},{"doi":"10.1001/jamadermatol.2026.2062","pmid":"42384418","title":"Topical Preparations for Moderate to Severe Rosacea Treatment","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2026-07-01T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13324944/","source_score":31,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-08T13:26:23.135Z","updated_at":"2026-07-08T13:26:23.135Z","tags":[{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"brand","value":"Soolantra","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"condition","value":"Rosacea","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"generic","value":"benzoyl peroxide","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"generic","value":"ivermectin","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"generic","value":"metronidazole","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"modality","value":"Topical Antimicrobial","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"modality","value":"Topical Antiparasitic","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"modality","value":"Topical Benzoyl Peroxide","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"sample_size","value":"n=11399","value_numeric":11399},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"warning","value":"'Encapsulated benzoyl peroxide' is a novel formulation; it may not yet have a widely recognized brand name confirmed in this paper.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"warning","value":"Full text is under PMC embargo until July 1, 2027; structured data is based solely on the abstract and results summary provided.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"warning","value":"The brand name 'Soolantra' is inferred for topical ivermectin 1% cream — not explicitly stated in the abstract.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.2062","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied based on the finding that ivermectin and encapsulated BPO outperform the long-standing standard metronidazole, but certainty of evidence grades from GRADE were not extractable from the abstract alone.","value_numeric":null}],"summaries":{"what_studied":"A systematic review and network meta-analysis of 32 RCTs (n=11,399 adults) compared the efficacy and tolerability of 10 topical therapies for moderate to severe rosacea, with most studies spanning 8–16 weeks of follow-up.","key_result":"Compared with metronidazole, both ivermectin (MD −4.17 lesions; 95% CI, 1.85–6.48) and encapsulated benzoyl peroxide (MD −4.14 lesions; 95% CI, 0.62–7.66) reduced lesion counts more effectively and achieved higher IGA success rates (+10.31% and +15.51%, respectively). However, encapsulated benzoyl peroxide had significantly more discontinuations due to adverse events than metronidazole (MD +8.33%; 95% CI, 0.45–16.22).","limitations":"- Follow-up was mostly 8–16 weeks, leaving long-term efficacy and tolerability unknown.\n- Limited data prevented robust synthesis of patient-reported outcomes and erythema endpoints.\n- Network meta-analysis relies on indirect comparisons, which may introduce uncertainty.","practice_takeaway":"For moderate to severe rosacea, topical ivermectin offers better lesion reduction and IGA response than metronidazole with a similar tolerability profile, making it a strong first-line topical option. Encapsulated benzoyl peroxide is also more efficacious but carries a higher risk of treatment discontinuation due to side effects — counsel patients accordingly before prescribing."}},{"doi":"10.1001/jamapediatrics.2026.2248","pmid":"42329656","title":"Obesity Management Pharmacotherapies and Lifestyle Treatment for Pediatric Obesity Management","journal_title":"JAMA Pediatrics","journal_issn":"2168-6203","published_at":"2026-06-22T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13288192/","source_score":28,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-01T13:27:05.864Z","updated_at":"2026-07-01T13:27:05.864Z","tags":[{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"age_group","value":"adolescent","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"age_group","value":"child","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"category","value":"Pediatrics","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"condition","value":"Pediatric Obesity","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"generic","value":"metformin","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"generic","value":"orlistat","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"generic","value":"phentermine-topiramate","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"modality","value":"Biguanide","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"modality","value":"Lifestyle Intervention","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"modality","value":"Lipase Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"modality","value":"Sympathomimetic-Anticonvulsant Combination","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"sample_size","value":"n=3835","value_numeric":3835},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"warning","value":"Age range (10–19 years) spans both child and adolescent categories; median age of 14.5 years suggests predominantly adolescent population.","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"warning","value":"Brand tag 'Ozempic' applied as a representative semaglutide brand; the specific formulation or brand studied may differ across included RCTs.","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"warning","value":"Full text is under PMC embargo until June 22, 2027; all extracted data are based solely on the published abstract.","value_numeric":null},{"paper_doi":"10.1001/jamapediatrics.2026.2248","tag_type":"warning","value":"Semaglutide combination results are derived from a limited number of studies — confidence intervals are wide and estimates should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and network meta-analysis compared the effectiveness of health behavior and lifestyle treatment (HBLT), obesity management pharmacotherapies (GLP-1 receptor agonists, metformin, orlistat, phentermine-topiramate), and their combinations on BMI, BMI z score, waist circumference, fat mass, and lean mass in children and adolescents aged 10–19 years with obesity across 42 RCTs (n=3,835) over typically 6–12 months.","key_result":"Semaglutide plus counseling produced the largest BMI reduction (MD −8.31; 95% CI −12.33 to −4.28) and BMI z score reduction (MD −1.80; 95% CI −2.39 to −1.21). All pharmacotherapies were more effective when paired with lifestyle treatment. HBLT alone also showed meaningful reductions vs. control (BMI MD −3.85; BMI z score MD −0.89).","limitations":"- Semaglutide combination estimates were based on a limited number of studies, reducing precision.\n- Outcomes reflect short-term follow-up (typically 6–12 months); long-term safety and sustainability data are limited.\n- Full text was under embargo; findings are based on the published abstract only.","practice_takeaway":"Combine pharmacotherapy (especially semaglutide) with structured lifestyle treatment for the greatest short-term weight reduction in adolescents with obesity. HBLT alone still delivers clinically meaningful BMI reduction and should remain the foundation of any treatment plan."}},{"doi":"10.1111/dom.70915","pmid":"42219271","title":"The Impact of\n GLP\n ‐1‐Based Therapies on Cardiovascular Outcomes in Type 2 Diabetes: A Comprehensive Systematic Review and Network Meta‐Analysis","journal_title":"Diabetes, Obesity and Metabolism","journal_issn":"1462-8902","published_at":"2026-05-31T00:00:00.000Z","url":"https://doi.org/10.1111/dom.70915","source_score":2,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-07T13:26:42.068Z","updated_at":"2026-06-07T13:26:42.068Z","tags":[{"paper_doi":"10.1111/dom.70915","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"condition","value":"Type 2 Diabetes Mellitus","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"generic","value":"albiglutide","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"generic","value":"efpeglenatide","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"sample_size","value":"n=97173","value_numeric":97173},{"paper_doi":"10.1111/dom.70915","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1111/dom.70915","tag_type":"warning","value":"Albiglutide was withdrawn from the market; its strong NMA profile may have limited practical relevance for current prescribing. Efpeglenatide is not widely approved in all markets—clinicians should verify local availability. The NMA includes indirect comparisons; most between-agent differences did not reach statistical significance, so agent-level rankings should be interpreted cautiously.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and frequentist random-effects network meta-analysis (NMA) evaluated agent-level cardiovascular outcomes of GLP-1-based therapies versus placebo (and each other) in adults with Type 2 diabetes, covering 15 RCTs through December 2025 and reporting hazard ratios for all-cause mortality, CV mortality, MACE, non-fatal MI, and non-fatal stroke.","key_result":"Across 15 trials (n=97,173), GLP-1-based therapies as a class significantly reduced all-cause mortality, CV mortality, and MACE versus placebo. In the NMA, efpeglenatide, albiglutide, and injectable semaglutide showed the most favorable MACE profiles; albiglutide significantly reduced non-fatal MI versus placebo; between-agent mortality differences were mostly non-significant.","limitations":"Most head-to-head between-agent comparisons in the NMA were not statistically significant, limiting conclusions about agent superiority. Non-fatal stroke estimates were imprecise across agents. The analysis is limited to RCTs with time-to-event data, which may not fully reflect real-world populations.","practice_takeaway":"GLP-1-based therapies, as a class, offer meaningful cardiovascular protection in adults with T2DM—clinicians can choose agents with confidence in class-level benefit. For MACE reduction specifically, injectable semaglutide and albiglutide show the strongest NMA profiles, which may inform agent selection in high-CV-risk patients."}},{"doi":"10.1111/dom.70884","pmid":"42209204","title":"Comparative Effects of Individual Glucagon‐Like Peptide‐1 Receptor Agonist‐Based Medications on Direct Measurement of Body Composition Among Adults With Overweight or Obesity With or Without Type 2 Diabetes: A Systematic Review and Network Meta‐Analysis of Randomised Controlled Trials","journal_title":"Diabetes, Obesity and Metabolism","journal_issn":"1462-8902","published_at":"2026-05-28T00:00:00.000Z","url":"https://doi.org/10.1111/dom.70884","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-08T13:46:42.435Z","updated_at":"2026-06-08T13:46:42.435Z","tags":[{"paper_doi":"10.1111/dom.70884","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"brand","value":"Mounjaro","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"brand","value":"Victoza","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"condition","value":"Overweight","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"condition","value":"Type 2 Diabetes","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"generic","value":"liraglutide","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"generic","value":"tirzepatide","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"sample_size","value":"n=3379","value_numeric":3379},{"paper_doi":"10.1111/dom.70884","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"warning","value":"Lean mass loss signal should be interpreted cautiously as absolute values and clinical significance (e.g., functional outcomes) were not reported in the available abstract.","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"warning","value":"The network meta-analysis includes indirect comparisons across trials with different body composition measurement techniques (e.g., DEXA, MRI, CT), which may introduce measurement heterogeneity not fully captured by the random-effects model.","value_numeric":null},{"paper_doi":"10.1111/dom.70884","tag_type":"warning","value":"Tirzepatide is a dual GIP/GLP-1 receptor agonist, not a pure GLP-1RA; the authors appear to have included it in this analysis, which may affect interpretation of GLP-1-specific effects.","value_numeric":null}],"summaries":{"what_studied":"This systematic review and network meta-analysis compared the effects of 17 individual GLP-1 receptor agonist (GLP-1RA) interventions or dosages on directly measured body composition outcomes (fat mass, VAT, SAT, liver fat, lean mass, etc.) in adults with overweight or obesity, with or without type 2 diabetes, across 43 RCTs (n=3,379) identified through November 2025.","key_result":"Subcutaneous GLP-1RAs significantly reduced total body fat, fat mass, VAT, SAT, and liver fat vs. control. No significant change in total lean tissue was found overall, but liraglutide 1.8 mg/day, semaglutide 1.0 mg weekly, and tirzepatide 15 mg weekly each significantly decreased lean mass (SMDs ranging from −0.50 to −1.09).","limitations":"- Total sample size (n=3,379 across 43 RCTs) is modest for a network meta-analysis with 17 interventions, limiting precision of indirect comparisons.\n- Variation in body composition measurement methods (e.g., DEXA, MRI, CT) across trials may introduce heterogeneity.\n- Duration and concurrent lifestyle interventions were not fully standardized across included RCTs, which may confound lean mass outcomes.","practice_takeaway":"GLP-1RAs — especially at higher doses — drive meaningful reductions in fat mass and visceral/liver fat, but clinicians should monitor for lean mass loss, particularly with liraglutide 1.8 mg/day, semaglutide 1.0 mg weekly, and tirzepatide 15 mg weekly. Pairing these agents with resistance exercise or protein optimization may help preserve muscle in patients on long-term therapy."}},{"doi":"10.1001/jamapsychiatry.2026.0658","pmid":"42090141","title":"Adjunctive Antipsychotics in Major Depressive Disorder","journal_title":"JAMA Psychiatry","journal_issn":"2168-622X","published_at":"2026-05-06T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13150735/","source_score":88,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-11","doi":"10.1001/jamapsychiatry.2026.0658","days":"7","issn":"2168-622X","rank":"8","field":"Clinical Medicine","score":"88","category":"Psychiatry","categories":["Psychiatry"],"_categories":["Psychiatry"]},"pubmed":{"doi":"10.1001/jamapsychiatry.2026.0658","title":"Adjunctive Antipsychotics in Major Depressive Disorder: A Systematic Review and Network Meta-Analysis.","journal":"JAMA psychiatry","methods":"","results":"$30","abstract":"$31","keywords":[],"pubmed_id":"42090141","conclusions":"","publication_date":"2026-05-06T00:00:00"},"crossref":{"DOI":"10.1001/jamapsychiatry.2026.0658","URL":"https://doi.org/10.1001/jamapsychiatry.2026.0658","ISSN":["2168-622X"],"link":[{"URL":"https://jamanetwork.com/journals/jamapsychiatry/articlepdf/2848529/jamapsychiatry_mcintyre_2026_oi_260019_1777303646.00799.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Adjunctive Antipsychotics in Major Depressive Disorder"],"author":[{"given":"Roger S.","family":"McIntyre","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}]},{"given":"Stephen M.","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuroscience, University of California, Riverside"}]},{"given":"Sung Ryul","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, Konyang University, Daejeon, Republic of Korea"}]},{"given":"Maurizio","family":"Pompili","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Mental Health, and Sensory Organs, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy"}]},{"given":"Joseph F.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York"}]},{"given":"Christoph U.","family":"Correll","sequence":"additional","affiliation":[{"name":"Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York"},{"name":"Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York"},{"name":"Charité–Universitätsmedizin Berlin, Berlin, Germany"}]},{"given":"Angela T. H.","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, German Center for Mental Health, partner site Berlin, Berlin, Germany"},{"name":"Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"}]},{"given":"Christine E.","family":"Dri","sequence":"additional","affiliation":[{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}]},{"given":"Heidi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada"},{"name":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada"}]},{"given":"Maj","family":"Vinberg","sequence":"additional","affiliation":[{"name":"The Early Multimodular Prevention and Intervention Research Institution, Psychiatric Centre North Zealand, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}]},{"given":"Taeho Greg","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Medicine, Yale University, New Haven, Connecticut"},{"name":"Department of Public Health Sciences, School of Medicine, University of Connecticut, Farmington"}]}],"issued":{"date-parts":[[2026,5,6]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":null,"created":{"date-time":"2026-05-06T15:31:22Z","timestamp":1778081482000,"date-parts":[[2026,5,6]]},"indexed":{"date-time":"2026-05-06T16:16:24Z","timestamp":1778084184274,"date-parts":[[2026,5,6]]},"subject":[],"abstract":"$32","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2848529"}},"subtitle":["A Systematic Review and Network 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Diclofenac had the broadest evidence, reducing both grade ≥2 and any-grade HFS (OR 0.30). Notably, mapisal *increased* HFS risk (OR 3.04). Silymarin ranked highest by SUCRA (0.91) but rests on limited trial data.","limitations":"- Silymarin's strong effect estimate comes from a single small trial and needs confirmation in a larger RCT.\n- Network meta-analysis relies on indirect comparisons; heterogeneity across trials in HFS grading and chemotherapy regimens may affect estimates.\n- Median age range is narrow (56–61 years), limiting generalizability to older or pediatric populations.","practice_takeaway":"For patients starting capecitabine, topical diclofenac has the strongest overall evidence for preventing clinically significant (grade ≥2) HFS and should be considered as a prophylactic option. 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(n=4,092) in adults with CT-confirmed non-cystic fibrosis bronchiectasis tested inhaled or oral anti-inflammatory agents vs placebo for ≥4 weeks, focusing on overall and severe exacerbation rates.","key_result":"Macrolides reduced overall exacerbations vs placebo (RR 0.44, 95% CI 0.35-0.56) and DPP-1 inhibitors did as well (RR 0.73, 95% CI 0.60-0.88; both moderate certainty); only DPP-1 inhibitors reduced severe exacerbations (RR 0.70, 95% CI 0.54-0.89). 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Upadacitinib 30 mg demonstrated the greatest efficacy across all endpoints, EASI-75 (OR = 12.3; 95% CrI 7.9-18.7), IGA-AD 0/1 (OR = 18.9; 95% CrI 12.0-29.7), and Itch NRS (OR = 11.1; 95% CrI 7.2-17.5), followed by upadacitinib 15 mg, abrocitinib 200 mg, and ivarmacitinib 8 mg. Baricitinib 2 mg and 4 mg consistently ranked lowest. SUCRA values confirmed upadacitinib 30 mg as the top performer (97%-98%).","abstract":"$36","keywords":["Bayesian network meta‐analysis","JAK inhibitors","abrocitinib","atopic dermatitis","baricitinib","ivarmacitinib","upadacitinib"],"pubmed_id":"41489415","conclusions":"Among oral JAKis, upadacitinib 30 mg, followed by upadacitinib 15 mg, achieved the most consistent short-term efficacy, providing superior skin clearance and itch relief. Abrocitinib 200 mg and ivarmacitinib 8 mg showed intermediate benefits, whereas baricitinib displayed modest effects. 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From Weeks 12 to 28, PASI responses with tildrakizumab increased from 60.77%→81.84% (PASI 75), 38.54%→71.23% (PASI 90), and 6.97%→22.64% (PASI 100); by Week 28, efficacy was comparable to TNFα, IL-17, IL-12/23, and other IL-23 inhibitors.","practice_takeaway":"For Asian adults starting tildrakizumab, expect slower early clearance by 12 weeks but marked gains by 28 weeks, reaching parity with other biologics. Its sustained improvement and low dosing frequency support it as an effective option for moderate-to-severe plaque psoriasis."}}],"initialOffset":17,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"study_design","value":"Systematic Review and Network Meta-Analysis"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Study Designs","href":"/hub/tag/study_design"},{"name":"Systematic Review and Network Meta-Analysis"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"study_design","hub_tag_value":"Systematic Review and Network Meta-Analysis"}}}]]

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