GLP-1-derived therapies and risk of sarcopenia: myth or reality?

Glucagon-like peptide-1 (GLP-1)-based therapies elicit a clinically significant reduction in body weight, an effect that correlates with improved clinical outcomes in individuals with type 2 diabetes and/or obesity. However, a risk of excessive reduction in skeletal muscle mass (SMM), potentially leading to sarcopenia, could minimize the benefit/risk balance of this pharmacological class.

Human studies that investigated the effects of GLP-1-based therapies on changes in SMM, muscle strength/function and muscle structure/quality.

Mixed results were reported, some studies emphasizing an excessive SMM loss while others not but arguing for a protective effect against sarcopenia through improved muscle quality (less myosteatosis). This controversy may stem from the misinterpretation of changes in body composition, as well as from the scarcity of studies that rigorously assess SMM, muscle function, and structure in humans. At present, no definitive conclusion can be drawn regarding the potential detrimental or beneficial effects of GLP-1-based therapies on skeletal muscle. Even if most available results are reassuring, further investigations are warranted, especially among individuals at higher risk of sarcopenia as older patients. In any case, the overall benefit/risk ratio of GLP-1-based therapies appears positive in most patients living with type 2 diabetes and/or clinical obesity.