Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 39719170 · doi:10.1016/j.metabol.2024.156113
What was done
A systematic review and random-effects pairwise and network meta-analysis of 22 randomized controlled trials (2,258 participants) identified via Medline, Embase, and Cochrane Library through November 12, 2024. The authors evaluated GLP-1 receptor agonists and GLP-1/GIP receptor dual agonists versus placebo or active comparators on total body weight, fat mass, and lean mass in adults with diabetes and/or overweight or obesity.
What was found
GLP-1RAs significantly reduced total body weight (MD -3.55 kg, 95% CI [-4.81, -2.29]), fat mass (MD -2.95 kg, 95% CI [-4.11, -1.79]), and absolute lean mass (MD -0.86 kg, 95% CI [-1.30, -0.42]). Lean mass loss comprised approximately 25% of total weight reduction, while relative lean mass (% change from baseline) was unaffected. Liraglutide (3.0 mg weekly or 1.8 mg daily) was the only agent to achieve significant weight reduction without significantly reducing lean mass. Tirzepatide (15 mg weekly) and semaglutide (2.4 mg weekly) achieved the greatest weight and fat mass reduction but were among the least effective in preserving lean mass.
Why it matters
This network meta-analysis quantifies that approximately one-quarter of incretin-induced weight loss consists of lean mass, showing that the most potent agents (tirzepatide and semaglutide) also induce the greatest absolute reductions in lean mass.
Limits
The abstract does not specify the body composition measurement modalities (e.g., DXA vs. BIA), trial durations, background dietary or exercise protocols, or whether lean mass loss translated into functional strength impairment.
Cited by
- context The majority of people using GLP-1 weight loss drugs lose significant muscle mass, and upon stopping the drug, nearly all the weight is regained without regaining the muscle.