GLP-1 Receptor Agonists Improve Relative Lean Mass but Cause Absolute Loss in Obesity Management

Managing obesity often involves significant weight loss, but a critical concern is the concomitant loss of lean muscle mass, which can negatively impact metabolic health, strength, and long-term outcomes. While GLP-1 receptor agonists (GLP1-RA) are highly effective for weight reduction, their precise impact on body composition, specifically the preservation or loss of lean mass, has not been fully elucidated. Understanding this effect is crucial for optimizing treatment strategies and ensuring that weight loss is healthy and sustainable, minimizing sarcopenia risk.

This systematic review and meta-analysis synthesized data from 7 randomized controlled trials (RCTs) involving 821 patients with obesity. Researchers compared the effects of GLP1-RA, administered at doses approved for obesity management, against placebo. The search encompassed PubMed, Embase, and LILACS up to March 2025. A random-effects model was employed to analyze changes in lean mass as a proportion of total weight, absolute lean mass, and percentage of lean mass, alongside adverse effects. The primary endpoints focused on quantifying these body composition changes.

GLP1-RA treatment significantly improved body composition by increasing lean mass as a proportion of total weight, showing an increase of 1.81% (95% CI: 1.1-2.52; p<0.00001; I²=7%). However, a significant decrease was observed in absolute lean mass, with an average loss of -1.74 kg (95% CI: -3.04 to -0.45; p<0.00001; I²=98%). The percentage of lean mass also decreased by -3.06% (95% CI: -5.10 to -1.02; p<0.00001; I²=98%).