Losing Weight, Losing Muscle? Muscle Health During GLP-1-Based Obesity Therapy

Vollständiger Abstract

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and related nutrient-stimulated hormone (NuSH) therapies have transformed obesity pharmacotherapy, delivering weight loss approaching that seen with bariatric surgery. However, concerns have emerged regarding loss of fat‑free mass, skeletal muscle mass, and possible sarcopenia. Reductions in lean mass occur during treatment with semaglutide and tirzepatide, but these changes are generally proportional to total weight loss and occur alongside greater reductions in fat mass, visceral adiposity, and ectopic lipid deposition. The clinical interpretation of lean mass loss is further complicated by limitations of dual-energy X-ray absorptiometry, which cannot distinguish contractile muscle from body water, organs, and connective tissue. Importantly, available data suggest that muscle quality and metabolic function may improve despite reductions in absolute lean mass. Overall, current evidence does not support disproportionate skeletal muscle loss during GLP-1-based obesity therapy. This review summarizes current evidence on GLP-1RA and NuSH-associated changes in muscle mass, discusses mechanisms, identifies populations at risk, and outlines practical strategies to preserve muscle health during treatment.