Muscle health in the modern era of incretin-based therapies

Intentional weight loss improves obesity-related outcomes but reduces lean body mass, raising concern about skeletal muscle mass, function and long-term health. GLP-1 receptor agonists (GLP-1RAs) produce clinically meaningful weight loss primarily by lowering energy intake and slowing gastric emptying, with additional benefits on insulin sensitivity and inflammation.

To clarify GLP-1RAs' effects on skeletal muscle tissue, body composition and physical function by reviewing preclinical and clinical evidence.

Across randomized and controlled studies, GLP-1RAs reduce fat mass more than lean body mass. Functional measures appear preserved. Preclinical and early clinical data suggest improvements in muscle quality (microvascular recruitment, mitochondrial efficiency, reduced intramuscular fat) rather than hypertrophy.

GLP-1RA-induced weight loss is largely fat mass with modest absolute lean body mass decline and no consistent deterioration in strength or function. Progressive resistance training, adequate/high-quality protein and periodic monitoring of body composition and performance should accompany therapy, especially in higher-risk patients.