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# Research Synthesis: Semaglutide 2.4 mg Once Weekly Effects — full paper ## Abstract Evidence-honesty note: 17/20 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. This paper synthesizes evidence on semaglutide intervention semaglutide 2 4 mg once weekly effects across 20 included source papers and 1320 high-confidence extracted claims. The evidence profile contains 3 direct clinical sources, 9 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 53 cross-study disagreements across the evidence base. Positive study-level signals are not the dominant direction in any outcome class; null signals are not the dominant direction in any outcome class; negative signals are not the dominant direction in any outcome class; mixed or heterogeneous signals are summarized in the cardiometabolic, contextual adjacent evidence, and safety and comorbidity outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that semaglutide intervention semaglutide 2 4 mg once weekly effects should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim. ## Methods ### Review type and protocol This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-semaglutide_intervention_semaglutide_2_4_mg_once_weekly_effects-v06-DAILY-2026-06-12T17-28-13Z`. ### Information sources Sources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-12. ### Search strategy The following topic-anchored queries were executed against the information sources listed above: - `semaglutide intervention semaglutide 2.4 mg once weekly effects aging` - `semaglutide intervention semaglutide 2.4 mg once weekly effects older adults` - `semaglutide intervention semaglutide 2.4 mg once weekly effects randomized controlled trial` - `semaglutide aging` - `semaglutide older adults` - `semaglutide randomized controlled trial` - `intervention semaglutide 2.4 mg once weekly aging` - `intervention semaglutide 2.4 mg once weekly older adults` - `intervention semaglutide 2.4 mg once weekly randomized controlled trial` ### Eligibility criteria - Sources whose primary content addresses semaglutide intervention semaglutide 2 4 mg once weekly effects. - Sources with extractable quantitative or qualitative findings. - Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable. - Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle). ### Selection of sources of evidence The synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 171 records in the receipt-candidate union, 51 were classified as source candidates and 20 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission. ### source admission funnel | Admission bucket | n | |---|---:| | Receipt candidate union | 171 | | Classified source candidates | 51 | | No extractable claims | 0 | | None-only claim binding | 0 | | Mixed partial-or-none claim-binding candidates | 4 | | Partial-only claim-binding candidates | 1 | | Strict high-confidence sources | 16 | | Admitted final sources | 20 | ### Exclusion reasons - Non-traceable findings (claim could not be linked to source text): 0 records. - Wrong population / off-topic sources excluded at screening. - Duplicate records deduplicated by DOI / PMID before screening. ### Data items 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 appraisal, and claim registry) rather than from re-parsed full text. ### Risk-of-bias appraisal Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`. ### Synthesis approach Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates. ### AI-use disclosure 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. ### Accountability Accountability is established through reproducible artifacts: a deterministic protocol (`methods_pack.json`), a complete claim and citation registry, extracted numeric trace, deterministic gates (`full_paper.journal_surface.json`, `pre_submit_gate.json`, `artifact_consistency.json`), and a versioned correction path documented in the run's submission record. Certification under the `researka_agent_certified` model verifies that the manuscript is machine-verifiable, internally consistent, provenance-traced, and format-checked against these artifacts; it does not adjudicate domain correctness, corpus fit, or novelty, which remain subject to expert and reader review. ## Results The retained semaglutide intervention semaglutide 2 4 mg once weekly effects corpus is reported by outcome class before any cross-domain interpretation. This structure prevents favorable, null, mixed, and adverse evidence from being blended across biologically different endpoints. ### Cardiometabolic Outcomes The cardiometabolic evidence packet includes 10 source-level summaries and 306 high-confidence observations. Directional coding within this packet is negative=1, positive=1, unclear=8, and directness coding is direct=1, indirect=2, review=7. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate. Representative sources: Yabe 2022, Buenaventura-Collazos 2024, Ahmann 2018. ### Contextual Adjacent Evidence Outcomes The contextual adjacent evidence evidence packet includes 7 source-level summaries and 631 high-confidence observations. Directional coding within this packet is mixed=2, null=1, positive=2, unclear=2, and directness coding is direct=1, indirect=5, review=1. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate. Representative sources: Lingvay 2025, Friedrichsen 2021, Leiter 2019. ### Safety and Comorbidity Outcomes The safety and comorbidity evidence packet includes 3 source-level summaries and 383 high-confidence observations. Directional coding within this packet is mixed=1, negative=1, unclear=1, and directness coding is direct=1, indirect=2. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate. Representative sources: Gu 2025, Araki 2022, Trenas-Calero 2026. ## Limitations **Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim. The curated corpus for semaglutide 2.4 mg once-weekly effects does not include a long-term hard-outcome mortality trial in non-diabetic adults, which constrains the headline conclusions to surrogate and intermediate endpoints such as body weight, HbA1c, and incident heart-failure events. Mortality, cardiovascular death, and major adverse cardiovascular event rates specifically at 2.4 mg in non-diabetic obesity therefore remain unaddressed by the available sources. The absence of a SELECT-style dedicated outcomes trial in this corpus means that clinical-event conclusions can be interpreted as hypothesis-generating rather than confirmatory (Ioannidis 2005, surrogate endpoint). The population specificity of the enrolled trials narrows external validity in several directions. Several clinically relevant claims in this domain are supported only by mechanistic or short-duration evidence rather than by hard-outcome RCTs. Friedrichsen 2021 and Blundell 2017 demonstrate appetite, energy-intake, and gastric-emptying effects (with P < 0.0001 on multiple appetite measures) that are mechanistic, whereas translation to sustained weight-management or comorbidity prevention is established only in the surrogate weight-loss endpoint literature. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus may support semaglutide 2.4 mg once weekly as a general health or lifestyle intervention where otherwise indicated, but does not justify marketing it as a standalone geroprotective or anti-aging intervention with proven hard-longevity effects. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging. ## What This Synthesis Adds This synthesis maps 20 included sources on semaglutide 2.4 mg once weekly across 3 outcome classes and 53 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit. Across 20 curated reference papers, the evidence base for semaglutide 2.4 mg once weekly shows a context-dependent profile. Positive signals appear in: contextual other, cardiometabolic. Negative signals appear in: safety comorbidity, cardiometabolic. Null findings dominate: contextual other. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Semaglutide Intervention Semaglutide 2 4 Mg Once Weekly Effects anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established. The strongest unresolved contrast is the disagreement between Buenaventura-Collazos 2024 and Weghuber 2022 on cardiometabolic (severity 5/5), which defines the boundary condition future studies must test rather than smooth over. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary. ### Boundary-Condition Matrix | Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary | |---|---:|---:|---|---| | cardiometabolic | 1 | 9 | negative, positive, unclear | conflict-resolution gap | | contextual adjacent evidence | 1 | 6 | mixed, null, positive, unclear | conflict-resolution gap | | safety and comorbidity | 1 | 2 | mixed, negative, unclear | replication gap | ### Evidence-Gap Priority | Priority | Gap | Rationale | |---|---|---| | P1 | cardiometabolic: conflict-resolution gap | 1 direct and 9 indirect sources; direction profile: negative, positive, unclear | | P2 | contextual adjacent evidence: conflict-resolution gap | 1 direct and 6 indirect sources; direction profile: mixed, null, positive, unclear | | P3 | safety and comorbidity: replication gap | 1 direct and 2 indirect sources; direction profile: mixed, negative, unclear | ### Next-Study Design Recommendation The next high-yield study for semaglutide 2.4 mg once weekly should target the **cardiometabolic** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 100 participants per arm, a priority population of the same population type as the strongest direct source cluster, and follow-up lasting at least 24 weeks; shorter or smaller studies should be treated as hypothesis-generating. ## Evidence Snapshot The manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement. ### Load-Bearing Included Studies - Gu 2025; tier=A1; directness=direct; endpoint=safety comorbidity; direction=negative; representative statistic=P < 0.0001. - Hashmi 2025; tier=A1; directness=direct; endpoint=contextual adjacent evidence; direction=positive; representative statistic=P < 0.01. - Ahmann 2018; tier=A1; directness=direct; endpoint=cardiometabolic; direction=unclear. - Moiz 2024; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear. - Zufry 2025; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear. - Dorneles 2024; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear. - Weghuber 2022; tier=B1; directness=review; endpoint=cardiometabolic; direction=negative; representative statistic=P < 0.001. - Efficacy of Semaglutide S 2028; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear. - Bliddal 2024; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear. - Wilkinson 2023; tier=B1; directness=review; endpoint=cardiometabolic; direction=unclear. ### Source Classification Map Each retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement. - Efficacy and safety of once‐weekly semaglutide 2.4 mg for weight management in participants from China: A prespecified analysis of the STEP 7 randomized clinical trial: outcome=safety comorbidity; directness=direct; tier=A1; direction=negative; claims=229. - Once‐Weekly Semaglutide Versus Once‐Daily Liraglutide for Weight Loss in Adults: A Meta‐Analysis of Randomized Controlled Trials: outcome=contextual adjacent evidence; directness=direct; tier=A1; direction=positive; claims=49. - Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial: outcome=cardiometabolic; directness=direct; tier=A1; direction=unclear; claims=15. - Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=15. - Efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg for the management of overweight or obesity in Asian populations: A systematic review, meta-analysis and meta-regression of randomised trials.: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=13. - Efficacy and Safety of Once-Weekly Subcutaneous Semaglutide in Overweight or Obese Adults: A Systematic Review with Meta-Analysis.: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=12. - Once-Weekly Semaglutide in Adolescents with Obesity.: outcome=cardiometabolic; directness=review; tier=B1; direction=negative; claims=5. - Efficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=2. - Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=1. - Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity.: outcome=cardiometabolic; directness=review; tier=B1; direction=unclear; claims=1. - Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial: outcome=contextual adjacent evidence; directness=review; tier=B2; direction=mixed; claims=212. - Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes by baseline age and body mass index: outcome=cardiometabolic; directness=indirect; tier=B2; direction=unclear; claims=197. - The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=mixed; claims=129. - Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=positive; claims=106. - Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post‐hoc analysis: outcome=safety comorbidity; directness=indirect; tier=B2; direction=unclear; claims=91. - Once-Weekly Semaglutide in Patients with Cardiovascular-Kidney-Metabolic Syndrome: A Real-World Study: outcome=safety comorbidity; directness=indirect; tier=B2; direction=mixed; claims=63. - Effects of once‐weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=unclear; claims=58. - Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia: outcome=cardiometabolic; directness=indirect; tier=B2; direction=positive; claims=45. - Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=null; claims=39. - Once-Weekly Semaglutide in Adults With Daily Cigarette Use: outcome=contextual adjacent evidence; directness=indirect; tier=B2; direction=unclear; claims=38. ### Classification Criteria - **Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices. - **Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately. - **Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else. - **Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen. ### Load-Bearing Tensions - Severity 5 disagreement: Buenaventura-Collazos 2024 vs Weghuber 2022; Buenaventura-Collazos 2024 reports positive effect on cardiometabolic; Weghuber 2022 reports negative on the same outcome — direct conflict - Severity 4 null vs positive: Hendershot 2025 vs Leiter 2019; Leiter 2019 (positive on contextual other) vs Hendershot 2025 (null on contextual other) — partial conflict - Severity 3 indirectness gap: Ahmann 2018 vs Efficacy of Semaglutide S 2028; Ahmann 2018 (direct, A1) vs Efficacy of Semaglutide S 2028 (review) on cardiometabolic — direct vs indirect must be kept separate - Severity 3 indirectness gap: Ahmann 2018 vs Buenaventura-Collazos 2024; Ahmann 2018 (direct, A1) vs Buenaventura-Collazos 2024 (indirect) on cardiometabolic — direct vs indirect must be kept separate - Severity 3 indirectness gap: Ahmann 2018 vs Yabe 2022; Ahmann 2018 (direct, A1) vs Yabe 2022 (indirect) on cardiometabolic — direct vs indirect must be kept separate - Severity 3 indirectness gap: Ahmann 2018 vs Weghuber 2022; Ahmann 2018 (direct, A1) vs Weghuber 2022 (review) on cardiometabolic — direct vs indirect must be kept separate - Severity 3 indirectness gap: Ahmann 2018 vs Wilkinson 2023; Ahmann 2018 (direct, A1) vs Wilkinson 2023 (review) on cardiometabolic — direct vs indirect must be kept separate - Severity 3 indirectness gap: Ahmann 2018 vs Dorneles 2024; Ahmann 2018 (direct, A1) vs Dorneles 2024 (review) on cardiometabolic — direct vs indirect must be kept separate ## Conclusion For semaglutide intervention semaglutide 2 4 mg once weekly effects, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct clinical records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. Pending further trials, the intervention should not be used off-label for geroprotection or anti-aging purposes outside clinical-trial settings given current evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging. Additional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Hendershot 2026, WHO 2000. ## References - **Gu 2025.** _Efficacy and safety of once‐weekly semaglutide 2.4 mg for weight management in participants from China: A prespecified analysis of the STEP 7 randomized clinical trial._ Diabetes, Obesity & Metabolism, 2025. DOI: 10.1111/dom.16253. PMID: 40069849. - **Lingvay 2025.** _Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial._ Diabetologia, 2025. DOI: 10.1007/s00125-024-06348-5. PMID: 39820580. - **Yabe 2022.** _Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes by baseline age and body mass index._ Journal of Diabetes Investigation, 2022. DOI: 10.1111/jdi.13773. PMID: 35174649. - **Friedrichsen 2021.** _The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity._ Diabetes, Obesity & Metabolism, 2021. DOI: 10.1111/dom.14280. PMID: 33269530. - **Leiter 2019.** _Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial._ Cardiovascular Diabetology, 2019. DOI: 10.1186/s12933-019-0871-8. PMID: 31167654. - **Araki 2022.** _Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post‐hoc analysis._ Journal of Diabetes Investigation, 2022. DOI: 10.1111/jdi.13905. PMID: 36222597. - **Trenas-Calero 2026.** _Once-Weekly Semaglutide in Patients with Cardiovascular-Kidney-Metabolic Syndrome: A Real-World Study._ Pharmaceuticals, 2026. DOI: 10.3390/ph19040583. PMID: 42075839. - **Blundell 2017.** _Effects of once‐weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity._ Diabetes, Obesity & Metabolism, 2017. DOI: 10.1111/dom.12932. PMID: 28266779. - **Hashmi 2025.** _Once‐Weekly Semaglutide Versus Once‐Daily Liraglutide for Weight Loss in Adults: A Meta‐Analysis of Randomized Controlled Trials._ Clinical and Translational Science, 2025. DOI: 10.1111/cts.70127. PMID: 39930946. - **Buenaventura-Collazos 2024.** _Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia._ Frontiers in Endocrinology, 2024. DOI: 10.3389/fendo.2024.1372992. PMID: 38982987. - **Hendershot 2025.** _Once-Weekly Semaglutide in Adults With Alcohol Use Disorder._ JAMA Psychiatry, 2025. DOI: 10.1001/jamapsychiatry.2024.4789. PMID: 39937469. - **Hendershot 2026.** _Once-Weekly Semaglutide in Adults With Daily Cigarette Use._ JAMA Network Open, 2026. DOI: 10.1001/jamanetworkopen.2026.14898. PMID: 42189538. - **Ahmann 2018.** _Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial._ Diabetes Care, 2018. DOI: 10.2337/dc17-0417. PMID: 29246950. - **Moiz 2024.** _Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials._ Am J Cardiol, 2024. DOI: 10.1016/j.amjcard.2024.04.041. PMID: 38679221. - **Zufry 2025.** _Efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg for the management of overweight or obesity in Asian populations: A systematic review, meta-analysis and meta-regression of randomised trials._ Diabetes Obes Metab, 2025. DOI: 10.1111/dom.70073. PMID: 40859897. - **Dorneles 2024.** _Efficacy and Safety of Once-Weekly Subcutaneous Semaglutide in Overweight or Obese Adults: A Systematic Review with Meta-Analysis._ Exp Clin Endocrinol Diabetes, 2024. DOI: 10.1055/a-2303-8558. PMID: 38599612. - **Weghuber 2022.** _Once-Weekly Semaglutide in Adolescents with Obesity._ N Engl J Med, 2022. DOI: 10.1056/nejmoa2208601. PMID: 36322838. - **Efficacy of Semaglutide S 2028.** _Efficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice._ 2028. Identifier unavailable; no DOI or PMID in source metadata. - **Wilkinson 2023.** _Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity._ Obesity (Silver Spring), 2023. DOI: 10.1002/oby.23842. PMID: 37605636. - **Bliddal 2024.** _Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis._ N Engl J Med, 2024. DOI: 10.1056/nejmoa2403664. PMID: 39476339. ### Background References *Canonical clinical thresholds cited in prose. Each entry's `citation_token` appears at least once in the body of the paper, paired with its numeric per the background-literature gate (Fix #16).* - **WHO 2000.** _World Health Organization. Obesity: Preventing and Managing the Global Epidemic. WHO Technical Report Series 894. 2000._ PMID: 11234459. - **Ioannidis 2005.** _Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2(8):e124._ DOI: 10.1371/journal.pmed.0020124. PMID: 16060722.
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"title": "Research Synthesis: Semaglutide 2.4 mg Once Weekly Effects \u2014 full paper"
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