Beyond Fat Loss: Addressing the Sarcopenia Challenge of Incretin-Based Therapies

Incretin-based therapies have transformed the treatment of type 2 diabetes mellitus and obesity by producing a weight-loss magnitude that was previously achievable only through intensive caloric restriction or bariatric surgery. This therapeutic shift has moved the clinical focus from the quantity of weight loss to the quality of weight loss. Lean mass reduction is frequently observed during weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs), dual glucose-dependent insulinotropic polypeptide/GLP-1RAs, or emerging multi-agonists. However, loss of lean body mass does not necessarily indicate equivalent loss of contractile skeletal muscle or sarcopenia. Incretin-based therapy is generally associated with preferential fat mass reduction, relative preservation of lean mass, and potential improvement in muscle quality through reduced myosteatosis. Thus, the clinically relevant question is whether incretin-associated body-composition changes lead to deterioration in muscle strength or physical performance, an increased risk of falls or fractures, or impaired quality of life. Available evidence does not show obvious functional harm; however, long-term data remain limited, especially in people with reduced muscle reserve. A muscle-conscious approach that integrates body-composition assessment, functional monitoring, resistance training, nutritional optimization, and emerging pharmacologic muscle-preserving strategies is needed to achieve high-quality weight loss.