Incretin-Based Obesity Medications Linked to Higher Muscle Loss

SAN FRANCISCO — Incretin-based obesity medications may result in higher muscle-related loss compared to other weight loss strategies, according to data published in Annals of Internal Medicine.

The findings suggest that while weight loss generally leads to known losses in muscle-based parameters, the proportion of muscle lost relative to total weight lost was higher in individuals taking incretin-based therapies. This difference was even more pronounced in studies using semaglutide and tirzepatide, two commonly prescribed medications in this class.

John A. Batsis, MD, an associate professor at the University of North Carolina at Chapel Hill, commented on the analysis during a presentation at the American College of Physicians Internal Medicine Meeting. He stated that the review did not identify any studies where incretin-based medications preserved muscle mass to a greater extent than placebo or lifestyle interventions alone.

The analysis, which reviewed data from human studies, highlights concerns about the impact of these medications on skeletal muscle health. While preclinical evidence has shown potential benefits of incretin-based therapies on muscle mass and metabolism, translation to human outcomes requires careful consideration of both body composition and functional outcomes, such as strength and mobility.

Experts note that weight loss-induced muscle loss is not unique to incretin-based medications. However, the observed increase in muscle loss relative to fat loss raises questions about the quality of weight reduction achieved with these drugs. Preserving skeletal muscle during weight loss is important for maintaining metabolic health, physical function, and long-term cardiovascular resilience.

Research published in Medicina supports the need for further investigation into how incretin-based therapies affect skeletal muscle in humans. While animal models suggest these medications may modulate muscle structure and metabolism, human data remain limited, and findings from clinical trials have shown variable effects on lean body mass.

Additional studies have indicated that incretin-based therapies are often accompanied by reductions in lean body mass, including skeletal muscle. This has prompted concern about potential risks such as sarcopenia, frailty, and diminished metabolic resilience, which could counteract some of the cardiovascular benefits associated with weight loss.

To mitigate muscle loss during weight loss, experts recommend combining pharmacological treatment with resistance training and adequate protein intake. Achieving ‘high-quality weight loss’ — defined as loss primarily from fat mass while preserving or enhancing muscle — may require lifestyle interventions alongside medication.

Ongoing research continues to evaluate the long-term effects of incretin-based medications on body composition, physical function, and cardiovascular outcomes. Until more data are available, clinicians are advised to monitor patients for changes in muscle mass and to incorporate strategies that support muscle preservation during obesity treatment.