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

Dec 16, 2025Current cardiology reports

Protecting Muscle Metabolism to Prevent Heart Disease in Obesity Treatments

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

25-40% of weight loss from incretin-based therapies may come from lean mass reduction.

Loss of skeletal muscle is a significant contributor to weight loss during incretin-based therapies.
Incretin therapies may enhance skeletal muscle quality by decreasing fat infiltration within the muscle.
The function and strength of skeletal muscle during these therapies is not well understood.
Exercise, protein intake, and creatine supplementation may help preserve muscle during weight loss.
Novel treatments like myostatin/activin inhibitors and selective androgen receptor modulators show potential in early trials.
Maintaining muscle mass during pharmacologic weight loss could support long-term metabolic and cardiovascular health.

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PURPOSE OF REVIEW: 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.

RECENT FINDINGS: 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.