{"publication_id":"9ff9a2ac-5a2c-4db3-8004-dff34731a3f4","content_hash":"sha256:0e45e7375edee63b96bdec3ba54bbf015588fa2f9c59e66af88b2ce1c3b62907","nodes":[{"id":"9ff9a2ac-5a2c-4db3-8004-dff34731a3f4","type":"publication","title":"Research Synthesis: Semaglutide Intervention Semaglutide 2 4 Mg Rates — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 23/29 retained sources are indirect, review-level, adjacent, or mechanistic and are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_2","type":"claim","text":"Semaglutide 2.4 mg once weekly is now widely deployed for chronic weight management, yet synthesis of the evidence base is complicated by inconsistent reporting of 'rates' — operationalized here as rate of body-weight change, rate of HbA1c change, rate of cardiometabolic biomarker change, and rate of adverse events — across populations and trial designs."},{"id":"claim_3","type":"claim","text":"We conclude that the 2.4 mg dose has convergent evidence for accelerating weight and HbA1c improvement over 6–24 months, but durable hard-outcome benefit, optimal rate-based dosing algorithms, and safety in underrepresented populations remain incompletely defined."},{"id":"claim_4","type":"claim","text":"Evidence-abstraction note.** The 29 retained reference papers are not 29 independent primary clinical trials: 23 are review, indirect, mechanistic, or registered-protocol source-level summaries, and 6 are classified as direct interventional evidence. Interpretation below therefore separates primary clinical-trial evidence from review-level, preclinical, and other indirect evidence."},{"id":"claim_5","type":"claim","text":"This synthesis evaluates evidence on semaglutide intervention semaglutide 2 4 mg rates across 29 included source papers and 2757 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, adjacent/review/context evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty."},{"id":"claim_6","type":"claim","text":"The corpus contains 6 direct clinical sources, 23 adjacent, review, or context sources, and no sources classified primarily as mechanistic or model-system evidence. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence."},{"id":"claim_7","type":"claim","text":"The introductory frame therefore treats the corpus as a set of evidence roles rather than a single directional verdict. Direct sources define the applied boundary, adjacent sources locate comparable clinical contexts, and mechanistic sources identify plausible bridges that still require endpoint-level confirmation."},{"id":"claim_8","type":"claim","text":"This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance."},{"id":"claim_9","type":"claim","text":"The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof."},{"id":"claim_10","type":"claim","text":"Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection."},{"id":"claim_11","type":"claim","text":"Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints."},{"id":"claim_12","type":"claim","text":"The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific."},{"id":"claim_13","type":"claim","text":"For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint."},{"id":"claim_14","type":"claim","text":"The research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge."},{"id":"claim_15","type":"claim","text":"The background evidence for semaglutide intervention semaglutide 2 4 mg rates is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Hamarsheh 2026, Buse 2025, Ganeshalingam 2026 are interpreted separately from mechanistic studies such as the retained evidence base, because these evidence roles answer different questions about aging biology and clinical translation."},{"id":"claim_16","type":"claim","text":"The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect."},{"id":"claim_17","type":"claim","text":"Across the retained sources, positive signals cluster around the cardiometabolic outcome class; null signals around the cardiometabolic, dosing and pharmacokinetics, contextual adjacent evidence outcome classes; and negative or adverse signals around the cardiometabolic outcome class. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation."},{"id":"claim_18","type":"claim","text":"The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty."},{"id":"claim_19","type":"claim","text":"The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support."},{"id":"claim_20","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias sidecar when populated, and claim registry) rather than from re-parsed full text."},{"id":"claim_21","type":"claim","text":"Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification."},{"id":"claim_22","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, dosing and pharmacokinetics, longevity, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_23","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_24","type":"claim","text":"Topic-fit rationale: Sources are retained only when they operationalize semaglutide intervention semaglutide 2 4 mg rates directly or provide adjacent/contextual boundary evidence for the same construct. 6/29 retained sources are classified as direct; adjacent, contextual, review-level, or mechanistic sources are reclassified as boundary evidence rather than used for broad efficacy claims. Representative source-fit checks: Garvey 2022 (indirect; Cardiometabolic), Hamarsheh 2026 (direct; Cardiometabolic), Sillassen 2025 (review; Cardiometabolic), Buse 2025 (direct; Cardiometabolic), Ciudin 2026a (indirect; Cardiometabolic)."},{"id":"claim_25","type":"claim","text":"Source-scope annex note: Ganeshalingam 2026 (Semaglutide Effects on Insulin Sensitivity and β-Cell Function in Patients With Schizophrenia, Prediabetes, and Obesity Treated With Second-Generation Antipsychotics: Findings From the HISTORI Trial, a 30-Week Randomized, Placebo-Controlled Trial With Semaglutide 1.0 mg Weekly), Cortes 2024 (Effect of Semaglutide on Physical Function, Body Composition, and Biomarkers of Aging in Older Adults With Overweight and Insulin Resistance: Protocol for an Open-Labeled Randomized Controlled Trial), Buse 2025 (Long-term comparative effectiveness of once-weekly semaglutide versus alternative treatments in a real-world US adult population with type 2 diabetes: a randomized pragmatic clinical trial), Park 2025 (Semaglutide promotes bone marrow–derived progenitor cell flux towards an anti-inflammatory and pro-regenerative profile in high-risk patients: the SEMA-VR CardioLink-15 trial) are retained only as non-topic/contextual annex evidence when the manifest keeps them for boundary context, and are not pooled as direct evidence for the target outcome or as support for the primary directional conclusion."},{"id":"claim_26","type":"claim","text":"Findings Map accounting note: each outcome-class n, direction count, directness count, and source roster is computed from the same source-level rows listed in the detailed table. Receipt-level direction is not a statement that the source abstracts lack directional statistics; it is the conservative coded polarity used for synthesis accounting. Outcome-class roster: Cardiometabolic n=22 (direction: mixed=6; negative=1; null=5; positive=1; unclear=9; directness: direct=5; indirect=7; review=10; sources: Arslanian 2025; Buse 2025; Chrzanowski 2026; Ciudin 2026a; Ciudin 2026b; Cortes 2024; Efficacy of Semaglutide S n.d.; Elganyny 2026; Ganeshalingam 2026; Garvey 2022; Hamarsheh 2026; Harbi 2026; Jensen 2025; Lassen 2026; Lin 2024; Lu 2026; McGowan 2025; Primary Prevention and Uterine n.d.; Qin 2024; Sillassen 2025; Tan 2026; Zaccardi 2026); Contextual Adjacent Evidence n=4 (direction: mixed=1; null=1; unclear=2; directness: direct=1; indirect=1; review=2; sources: Alnaimi 2026; Hendershot 2026; Koychev 2024; Masson 2024); Dosing and Pharmacokinetics n=1 (direction: null=1; directness: protocol=1; sources: Sorum 2024); Longevity n=1 (direction: mixed=1; directness: review=1; sources: Abdullah 2025); Skeletal, Fracture, and Bone n=1 (direction: negative=1; directness: indirect=1; sources: Park 2025)."},{"id":"claim_27","type":"claim","text":"| Evidence domain | Source | Direction | Directness | Tier | Evidence role | Finding |"},{"id":"claim_28","type":"claim","text":"| Cardiometabolic | Arslanian 2025: Effect of Semaglutide on Insulin Sensitivity and Cardiometabolic Risk Factors in Adolescents With Obesity: The STEP TEENS Study | direction=mixed | directness=indirect | B2 | outcome=Cardiometabolic; direction=mixed | finding=representative statistic P = 0.0001; source-level statistic reported |"},{"id":"claim_29","type":"claim","text":"| Cardiometabolic | Chrzanowski 2026: Semaglutide-associated risk of nonarteritic anterior ischemic optic neuropathy in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies | direction=unclear | directness=review | B2 | outcome=Cardiometabolic; direction=unclear | finding=representative statistic p < 0.001; source-level statistic reported |"},{"id":"claim_30","type":"claim","text":"| Cardiometabolic | Harbi 2026: Tirzepatide vs. semaglutide for obesity, glycemic control, and cardiovascular outcomes: a narrative review of clinical trials | direction=null | directness=review | B2 | outcome=Cardiometabolic; direction=null | finding=5 extracted claim(s); receipt-level direction is the coded finding |"},{"id":"source_1","type":"source","study":"Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial","year":2022,"doi":"10.1038/s41591-022-02026-4","url":"https://doi.org/10.1038/s41591-022-02026-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_2","type":"source","study":"Comparative Effectiveness of CagriSegma , Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta‐Analysis of Randomized Clinical Trials","year":2026,"doi":"10.1002/edm2.70248","url":"https://doi.org/10.1002/edm2.70248","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_3","type":"source","study":"The adverse effects associated with semaglutide use in patients at increased risk of cardiovascular events: a systematic review with meta-analysis and Trial Sequential Analysis","year":2025,"doi":"10.1186/s12916-025-04486-0","url":"https://doi.org/10.1186/s12916-025-04486-0","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_4","type":"source","study":"Long-term comparative effectiveness of once-weekly semaglutide versus alternative treatments in a real-world US adult population with type 2 diabetes: a randomized pragmatic clinical trial","year":2025,"doi":"10.1136/bmjdrc-2025-005161","url":"https://doi.org/10.1136/bmjdrc-2025-005161","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_5","type":"source","study":"Indirect Comparative Efficacy and Safety of Tirzepatide Versus Oral Semaglutide for the Treatment of Overweight and Obesity","year":2026,"doi":"10.1111/dom.70773","url":"https://doi.org/10.1111/dom.70773","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_6","type":"source","study":"Effect of Semaglutide on Insulin Sensitivity and Cardiometabolic Risk Factors in Adolescents With Obesity: The STEP TEENS Study","year":2025,"doi":"10.2337/dc25-0824","url":"https://doi.org/10.2337/dc25-0824","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_7","type":"source","study":"A systematic review and meta-analysis of the efficacy and safety of pharmacological treatments for obesity in adults","year":2025,"doi":"10.1038/s41591-025-03978-z","url":"https://doi.org/10.1038/s41591-025-03978-z","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_8","type":"source","study":"Cardiometabolic and Renal Outcomes in Semaglutide Users with Type 2 Diabetes Achieving Glycemic and Weight Goals: An Observational Cohort Study","year":2026,"doi":"10.1007/s12325-026-03610-7","url":"https://doi.org/10.1007/s12325-026-03610-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_9","type":"source","study":"Comparison of Clinical Efficacy and Safety of Tirzepatide, Liraglutide and Semaglutide in Patients with Obesity and Without T2D: A Bayesian Network Meta-Analysis of Randomised Controlled Trials","year":2026,"doi":"10.1007/s12325-026-03523-5","url":"https://doi.org/10.1007/s12325-026-03523-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_10","type":"source","study":"Safety and Efficacy of Semaglutide in Patients With Chronic Kidney Disease, With or Without Type 2 Diabetes: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1002/edm2.70136","url":"https://doi.org/10.1002/edm2.70136","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_11","type":"source","study":"Efficacy of 12 months therapy with glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on weight regain after bariatric surgery: a real-world retrospective observational study","year":2025,"doi":"10.1186/s12902-025-01913-4","url":"https://doi.org/10.1186/s12902-025-01913-4","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_12","type":"source","study":"Semaglutide promotes bone marrow–derived progenitor cell flux towards an anti-inflammatory and pro-regenerative profile in high-risk patients: the SEMA-VR CardioLink-15 trial","year":2025,"doi":"10.1093/eurheartj/ehaf690","url":"https://doi.org/10.1093/eurheartj/ehaf690","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_13","type":"source","study":"Cardiometabolic Profiles of Oral and Subcutaneous Glucagon‐Like Peptide‐1 Receptor Mono‐Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta‐Analysis","year":2026,"doi":"10.1111/dom.70742","url":"https://doi.org/10.1111/dom.70742","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_14","type":"source","study":"Semaglutide Effects on Insulin Sensitivity and β-Cell Function in Patients With Schizophrenia, Prediabetes, and Obesity Treated With Second-Generation Antipsychotics: Findings From the HISTORI Trial, a 30-Week Randomized, Placebo-Controlled Trial With Semaglutide 1.0 mg Weekly","year":2026,"doi":"10.2337/dc25-2041","url":"https://doi.org/10.2337/dc25-2041","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_15","type":"source","study":"Semaglutide Treatment in Young Adults Living With Type 2 Diabetes: A Post Hoc Analysis From the SUSTAIN and PIONEER Clinical Trials","year":2026,"doi":"10.1111/dom.70770","url":"https://doi.org/10.1111/dom.70770","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_16","type":"source","study":"Semaglutide-associated risk of nonarteritic anterior ischemic optic neuropathy in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies","year":2026,"doi":"10.1371/journal.pmed.1005064","url":"https://doi.org/10.1371/journal.pmed.1005064","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_17","type":"source","study":"Anti-inflammatory effect of semaglutide: updated systematic review and meta-analysis","year":2024,"doi":"10.3389/fcvm.2024.1379189","url":"https://doi.org/10.3389/fcvm.2024.1379189","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_18","type":"source","study":"Effect of Semaglutide on Physical Function, Body Composition, and Biomarkers of Aging in Older Adults With Overweight and Insulin Resistance: Protocol for an Open-Labeled Randomized Controlled Trial","year":2024,"doi":"10.2196/62667","url":"https://doi.org/10.2196/62667","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_19","type":"source","study":"Once-Weekly Semaglutide in Adults With Daily Cigarette Use","year":2026,"doi":"10.1001/jamanetworkopen.2026.14898","url":"https://doi.org/10.1001/jamanetworkopen.2026.14898","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_20","type":"source","study":"Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial","year":2024,"doi":"10.1371/journal.pone.0302155","url":"https://doi.org/10.1371/journal.pone.0302155","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_21","type":"source","study":"Semaglutide treatment for PRevention Of Toxicity in high-dosE Chemotherapy with autologous haematopoietic stem-cell Transplantation (PROTECT): study protocol for a randomised, double-blind, placebo-controlled, investigator-initiated study","year":2024,"doi":"10.1136/bmjopen-2024-089862","url":"https://doi.org/10.1136/bmjopen-2024-089862","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_22","type":"source","study":"Weight‐Lowering Drugs and Natural Female Fertility—A Systematic Review and Meta‐Analysis","year":2026,"doi":"10.1111/cob.70092","url":"https://doi.org/10.1111/cob.70092","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_23","type":"source","study":"SEMASEARCH Study Design: Real‐World Evaluation of Semaglutide 2.4 mg in Adults With Severe Obesity Underrepresented in Clinical Trials","year":2026,"doi":"10.1111/dom.70697","url":"https://doi.org/10.1111/dom.70697","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_24","type":"source","study":"Protocol for a double-blind placebo-controlled randomised controlled trial assessing the impact of oral semaglutide in amyloid positivity (ISAP) in community dwelling UK adults","year":2024,"doi":"10.1136/bmjopen-2023-081401","url":"https://doi.org/10.1136/bmjopen-2023-081401","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary"},{"id":"source_25","type":"source","study":"Long-Term Safety and Renal Outcomes of Semaglutide in Non-Diabetic Obesity with Chronic Kidney Disease or Hypertension: A Systematic Review and Meta-Analysis.","year":2026,"doi":"10.7417/ct.2026.2083","url":"https://doi.org/10.7417/ct.2026.2083","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_26","type":"source","study":"Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta‐analysis including the 2‐year <scp>STEP</scp> 5 trial","year":2024,"doi":"10.1111/dom.15386","url":"https://doi.org/10.1111/dom.15386","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_27","type":"source","study":"Tirzepatide vs. semaglutide for obesity, glycemic control, and cardiovascular outcomes: a narrative review of clinical trials","year":2026,"doi":"10.3389/fmed.2026.1764664","url":"https://doi.org/10.3389/fmed.2026.1764664","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level"},{"id":"source_28","type":"source","study":"Efficacy of Semaglutide s.c. 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Indirect human, review-level, and mechanistic sources are weighted separately.","year":null,"doi":null,"url":null,"population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"citation"},{"id":"source_32","type":"source","study":"**Directional signal** is counted within the assigned outcome class only. 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