Preserving the Metabolic Engine: Muscle as the Therapeutic Target for Cardiovascular Prevention in Obesity Pharmacotherapy

This review examines the impact of incretin-based therapies and related incretin therapies on skeletal muscle health during pharmacologic weight loss. It explores the extent to which lean mass reduction contributes to total weight loss and highlights strategies to preserve muscle as a determinant of cardiovascular resilience.

Emerging data indicate that 25–40% of incretin-based therapies-induced weight loss derives from loss of lean mass, with skeletal muscle being a key component. Although incretin-based therapies may improve the quality of skeletal muscle by reducing muscle fat infiltration, its function and strength remain underexplored. Exercise, adequate protein intake, and creatine supplementation mitigate these effects, whereas novel adjuncts such as myostatin/activin inhibitors and selective androgen receptor modulators show promise in early trials.

Preserving muscle during incretin-based pharmacotherapy weight reduction is key to sustain long-term metabolic and cardiovascular benefits. Future trials should assess body composition, functional outcomes, and integrate muscle-preserving co-therapies into obesity management.