Effect of GLP-1 receptor agonists on body composition

Obesity is present in up to 85% of individuals with type 2 diabetes mellitus (T2DM) and poses a major therapeutic challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for T2DM, are now widely used for obesity management and increasingly recognized for their impact on body composition beyond weight reduction. This review summarizes evidence on the effects of GLP-1RAs, particularly semaglutide and liraglutide, on fat mass, lean body mass (LBM), visceral adipose tissue (VAT), and resting energy expenditure (REE).

Clinical trials and meta-analyses show GLP-1RAs achieve marked fat mass loss, preferentially reducing VAT, with modest proportional declines in LBM. Despite reductions in absolute LBM, relative preservation or improvement is observed, and REE is largely maintained, with some reports of increases during prolonged therapy. In both diabetic and nondiabetic populations, GLP-1RAs improve metabolic health without accelerating sarcopenia. Rodent data support protective muscle effects through anti-inflammatory and myogenic mechanisms. Withdrawal, however, predictably results in weight regain, primarily as fat mass, highlighting the importance of continued therapy or supportive lifestyle strategies.

GLP-1RAs confer favourable body composition outcomes, with clinical implications for obesity, sarcopenic obesity, and broader metabolic disease management.