GLP-1-Based Pharmacotherapies and Skeletal Muscle Health in Obesity: A Narrative Review of Body Composition, Muscle Function, and Sarcopenia-Related Outcomes.

Background

Obesity is associated with impaired skeletal muscle health and sarcopenic obesity. GLP-1-based pharmacotherapies induce weight loss, but accompanying reductions in fat-free or lean mass raise concerns about skeletal muscle loss. Conversely, reductions in adiposity, inflammation, insulin resistance, and intramuscular fat may be beneficial.

Objective

This narrative review evaluated the effects of GLP-1-based pharmacotherapies on body composition, muscle quantity, composition and function, and their potential role in sarcopenia.

Methods

PubMed and Google Scholar were searched for clinical and experimental studies published primarily between 2016 and 2026.

Results

Preclinical studies identified potentially protective mechanisms, including improved insulin sensitivity, reduced inflammation, and modulation of mitochondrial function and protein turnover, but some also indicated muscle loss or proteolysis. Clinical studies reported greater reductions in fat mass than in fat-free or lean mass, neither of which represents skeletal muscle exclusively. Direct muscle and functional outcomes were assessed in few studies and yielded mixed results. Incident sarcopenia was rarely evaluated.

Conclusions

GLP-1-based pharmacotherapies may influence sarcopenia risk through competing pathways. Metabolic improvements may support muscle health, whereas energy restriction, inadequate protein intake, gastrointestinal adverse effects, and lean tissue loss may increase vulnerability. Current evidence is insufficient to determine their net effect on sarcopenia risk.