Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans.

This study investigated whether GLP-1 receptor agonist medicines cause disproportionate loss of lean body mass (LBM) or skeletal muscle in the context of obesity-related weight loss. Researchers conducted four pre-clinical studies in obese mice and a proof-of-concept clinical trial in humans (registered as NCT05606471). In obese mice, GLP-1 medicines primarily reduced body fat, with a small but statistically significant decrease in LBM. Notably, liver mass loss exceeded muscle mass loss among lean tissues. Although absolute muscle mass and strength declined, relative muscle mass and strength improved, leading to better running performance. The study also found that muscle atrophy during immobilization was similar regardless of treatment, but GLP-1 medicines produced a distinct muscle proteome signature compared to calorie restriction alone. In the human trial, patients with obesity treated with GLP-1 medicines showed improved body composition without negative effects on strength. The authors conclude that, in middle-aged mice and humans, GLP-1 medicines slightly reduce absolute muscle values but positively affect overall body composition and mobility. Limitations include the proof-of-concept (small-scale) nature of the clinical component and the use of animal models as a primary evidence base.

Why this grade: The evidence is mixed: the bulk of the data comes from animal studies, and the human component is described only as a proof-of-concept clinical trial, limiting the strength of conclusions that can be drawn for humans alone.