Semaglutide

ID: semaglutide

Aliases: Wegovy, Ozempic, SEMAGLUTIDE

Type: compound

Route/form: subcutaneous injection; oral tablet formulation also exists

Status: approved

Evidence level: approved / labelled

Best data tier: approved label + human controlled/review

Support scope: human, context

Source types: company, human_physiology, human_rct, label, meta_analysis, systematic_review

Linked sources: 10

Broad outcomes: Cardiovascular / lipids / blood pressure, Fat loss / metabolic health, Muscle growth / performance / recovery

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• GLP-1 receptor agonist

Optimization domains

• metabolic
• obesity
• diabetes
• cardiometabolic
• body composition
• GLP-1 adjunct

Research basis

• Large randomized human obesity trials and meta-analyses show clinically meaningful weight loss in adults with overweight/obesity, while SELECT adds cardiovascular-outcome evidence in people with obesity and established cardiovascular disease without diabetes.
• Human appetite/energy-intake physiology helps explain the weight-loss signal beyond simply naming the GLP-1 receptor.
• Body-composition reviews and GLP-1 adjunct trials make semaglutide a reference comparator for the lean-mass-preservation question rather than a muscle-preserving drug itself.

Limits, risks, and missing evidence

• GI intolerance, gallbladder/pancreatitis warnings, dehydration/renal issues, and discontinuation weight regain remain practical constraints.
• Weight loss includes lean mass; semaglutide is not a direct anabolic, mitochondrial, or performance drug.
• Meta-analyses support efficacy but do not remove the need to interpret dose, duration, diabetes status, baseline obesity, and concurrent resistance training/protein intake.

Risk flags

• prescription
• metabolic endocrine
• medical supervision

Linked papers, labels, and reviews

1. Once-Weekly Semaglutide in Adults with Overweight or Obesity
   human_rct / pubmed_semaglutide_step1_2021
   STEP 1 trial.
2. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
   human_rct / pubmed_semaglutide_select_2023
   SELECT cardiovascular outcomes trial; direct human evidence in obesity without diabetes, adding hard-outcome context beyond weight-loss trials.
3. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity
   human_physiology / pubmed_semaglutide_appetite_energy_2017
   Human appetite and energy-intake physiology study; helps explain why semaglutide works beyond a generic GLP-1 label.
4. A systematic review of the effect of semaglutide on lean mass: insights from clinical trials
   systematic_review / pubmed_semaglutide_lean_mass_review_2024
   Lean-mass/body-composition context for interpreting GLP-1 weight loss rather than treating scale loss as pure fat loss.
5. Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition
   meta_analysis / pubmed_glp1_body_composition_network_meta_2025
   Network meta-analysis comparing body-composition effects across GLP-1 receptor agonists and co-agonists.
6. DailyMed label: WEGOVY semaglutide injection
   label / dailymed_wegovy_label
   Official semaglutide obesity-label context for subcutaneous route, titration, contraindications, and adverse-effect warnings.
7. Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial
   human_rct / pmc_bimagrumab_semaglutide_phase2_2026
   Peer-reviewed BELIEVE phase 2 obesity trial testing IV bimagrumab, SC semaglutide, and combinations; relevant to fat-share of weight loss, lean-mass preservation, muscle-spasm tolerability, and combination-therapy questions.
8. Results from Phase 2 COURAGE Trial Demonstrating Potential to Improve Quality of GLP-1 receptor agonist-induced Weight Loss by Preserving Lean Mass, Presented at EASD
   company / regeneron_courage_easd_2025
   Sponsor-reported 26-week COURAGE phase 2 obesity results: semaglutide 2.4 mg plus trevogrumab with or without garetosmab shifted weight-loss composition toward fat mass; not a peer-reviewed paper at this curation point.
9. Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis
   meta_analysis / pubmed_semaglutide_obesity_meta_2023
   RCT meta-analysis in adults with obesity/overweight without diabetes; supports weight-loss efficacy and GI/discontinuation safety framing beyond a single STEP trial.
10. 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
    meta_analysis / pubmed_semaglutide_longterm_obesity_meta_2024
    Longer-duration RCT meta-analysis of semaglutide 2.4 mg in overweight/obesity without diabetes; useful for durability and safety synthesis.