Glucagon-like peptide-1 (GLP-1)-based therapies have gained attention for their ability to significantly reduce body weight, which correlates with improved clinical outcomes in individuals with type 2 diabetes and obesity. However, there is a growing concern regarding the potential risk of excessive reduction in skeletal muscle mass (SMM), which could lead to sarcopenia, a condition characterized by severe loss of muscle mass, strength, and function.
Areas Covered
This review discusses various human studies that have investigated the effects of GLP-1-based therapies on SMM, muscle strength, function, and muscle structure/quality. The findings from these studies have been mixed, with some indicating a significant loss of SMM while others suggest a protective effect against sarcopenia through improved muscle quality, specifically a reduction in myosteatosis.
The controversy surrounding these findings may arise from the misinterpretation of changes in body composition and the limited number of studies that rigorously assess SMM and muscle function in humans. As such, no definitive conclusions can currently be drawn regarding the potential detrimental or beneficial effects of GLP-1-based therapies on skeletal muscle.
Despite the mixed results, most available data appear reassuring. While some muscle mass reduction may occur, it does not seem disproportionate compared to other weight loss therapies. Additionally, improvements in muscle quality due to reduced fat infiltration in skeletal muscle have been reported, suggesting that muscle strength, function, and performance may not be adversely affected by GLP-1RA therapy.
Nonetheless, further investigations are warranted, particularly among populations at higher risk of sarcopenia, such as older individuals and frail patients with severe comorbidities. Until more conclusive data are available, the overall benefit/risk ratio of GLP-1-based therapies remains positive for most patients living with type 2 diabetes and/or clinical obesity.
What this study does not show
This review does not provide definitive evidence regarding the impact of GLP-1 therapies on skeletal muscle mass or the risk of sarcopenia, as the studies reviewed yield mixed results.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established
The evidence is based on a review of various studies examining GLP-1 therapies and their effects on muscle mass and function.