Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review
Authors' conclusion
Glucagon-like peptide-1 receptor agonists demonstrate substantial weight loss in adults without diabetes, with an expanding range of therapeutic options, including oral and multiagonist therapies.
Study context
- Population
- Adults with overweight or obesity without diabetes; RCTs with treatment duration ≥16 weeks
- Participants
- 25,816 adults38 RCTs
- Comparison
- GLP-1 RAs and co-agonists vs placebo
- Outcome
- Placebo-subtracted weight loss (up to)
Methodological detailsupdate of prior systematic review, no quantitative synthesis (heterogeneity)
- Update of prior systematic review
- No quantitative synthesis (heterogeneity)
Pooled result
As reported in the abstract
Placebo-subtracted weight loss
- Liraglutide
- −5.8% (95% CI −8.0% to −3.6%)
- Subcutaneous semaglutide
- −14.8% (95% CI −16.2% to −13.4%)
- Oral semaglutide
- −14.3% (95% CI −17.2% to −11.4%)
- Orforglipron
- −12.4% (95% CI −15.1% to −9.7%)
- Tirzepatide
- −19.0% (95% CI −21.6% to −16.4%)
- Amycretin
- −23.9% (95% CI −29.3% to −18.5%)
- Retatrutide
- −22.1% (95% CI −24.9% to −19.3%)
Further pooled results
Head-to-head weight loss
- Greater weight loss with semaglutide and JNJ-64565111 than liraglutide
- Greater weight loss with tirzepatide and cagrilintide-semaglutide (CagriSema) than semaglutide
Safety
AEs, GLP-1 RA vs placebo · value = gastrointestinal AEs · Safety outcomes inconsistently reported
Discontinuation due to AEs
Serious AEs
Deaths
Adverse events (AEs), GLP-1 RA vs placebo
- No new safety signals; discontinuation numerically higher with some oral agents
Original publication
Efficacy and Safety of Glucagon-like Peptide-1 Receptor Agonists and Co-agonists for Weight Loss Among Adults Without Diabetes : An Updated Systematic Review. Ann Intern Med. Published 1 September 2026. doi:10.
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