Weight Loss With GLP ‐1 Agonists in Nondiabetic Adults: Systematic Review and Network Meta‐Analysis
Authors' conclusion
Tirzepatide, particularly at higher doses, provides the greatest weight reduction in adults without diabetes. Future studies should evaluate discontinuation, weight regain, metabolic outcomes, cost-effectiveness, and patient preferences.
Study context
- Population
- Adults (≥18 years) with obesity without T2D, phase 3 randomized controlled trials (RCTs) with at least one arm of tirzepatide, semaglutide or liraglutide; search to May 2025
- Participants
- 14,059 adults15 RCTs
- Comparison
- Tirzepatide vs semaglutide vs liraglutide vs placebo
- Outcome
- Body weight reduction
Methodological detailsfrequentist random-effects network meta-analysis, phase 3 RCTs
- Frequentist random-effects network meta-analysis
- Phase 3 RCTs
Pooled result
As reported in the abstract
- All agents significantly reduced body weight vs placebo
- Ranking of reduction: tirzepatide maximum tolerated dose > tirzepatide 15 mg > 10 mg > semaglutide 2.4 mg > tirzepatide 5 mg > liraglutide 3 mg
Safety
- Tirzepatide and semaglutide associated with higher risk of any adverse event vs placebo; liraglutide was not
Original publication
Weight Loss With GLP ‐1 Agonists in Nondiabetic Adults: Systematic Review and Network Meta‐Analysis. Obesity (Silver Spring). Published 5 April 2026. doi:10.
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