Effect of GLP-1 receptor agonists at doses for obesity management on muscle health: systematic review and meta-analysis of randomized controlled trials (RCTs)

Introduction The impact of GLP-1 receptor agonists (GLP1-RA) treatment on lean mass and body composition in patients with obesity is not fully understood. Methodology Systematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo. Search was conducted in PubMed, Embase, and LILACS in March 2025. A meta-analysis was performed using a random-effects model to evaluate the change in lean mass as a proportion of total weight, the absolute and relative changes in lean mass, and adverse effects. Results Seven studies (821 patients) were included in the analysis. GLP1-RA significantly improved lean mass as a proportion of total weight, with an observed increase of 1.81% (95% CI: 1.1– 2.52; p < 0.00001; I ² = 7%). However, a significant decrease was observed in the absolute change in lean mass (−1.74 kg; 95% CI: −3.04 to −0.45; p < 0.00001; I ² = 98%) and in the percentage of lean mass (−3.06%; 95% CI: −5.10 to −1.02; p < 0.00001; I ² = 98%). Semaglutide demonstrated the most significant reduction in absolute lean mass, with a loss of −5.44 kg (95% CI: −7.07 to −3.81; p < 0.00001). Conclusions There is an improvement in body composition due to an increase in lean mass as a proportion of total weight, an effect that could be amplified with the use of semaglutide. Our results suggest that lean mass loss should not be considered a limitation for the use of these drugs in patients with obesity. However, it is essential to accompany drug treatment with nutritional and physical exercise interventions to preserve or improve muscle mass and optimize clinical outcomes.