Effects of Semaglutide and Tirzepatide on Skeletal Muscle Mass and Sarcopenia Risk in Adults With Obesity or Overweight: A Narrative Review

Background: GLP-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP agonists are highly effective therapies for obesity management. However, associated reductions in lean body mass have raised concerns regarding sarcopenia risk. This review evaluated whether these changes translate into clinically relevant sarcopenia or sarcopenic obesity. Methods: A narrative review of the PubMed, Cochrane Library and Google Scholar databases was conducted up to May 2026, to evaluate GLP-1 receptor agonist effects on muscle mass, body composition, and sarcopenia-related outcomes. Results: GLP-1 RAs produced substantial weight loss, with lean mass accounting for approximately 20–33% of total weight reduction, a proportion comparable to that reported with lifestyle and surgical interventions. Most studies reported preserved or improved muscle function despite reductions in lean mass. MRI studies demonstrated reduced intramuscular fat with only modest decreases in muscle volume. However, one retrospective study in older adults with type 2 diabetes reported concurrent declines in muscle mass and function, suggesting increased vulnerability in high-risk populations. Conclusions: Current evidence does not support a uniformly increased risk of sarcopenia or sarcopenic obesity during GLP-1 RA therapy. Lean mass loss appears largely proportional to overall weight reduction and is generally not accompanied by clinically meaningful declines in muscle function. Older adults and individuals with low baseline muscle reserve may require closer monitoring.