GLP-1-derived therapies and sarcopenia: plea for a specific focus on at risk special populations

A risk of excessive reduction in skeletal muscle mass (SSM), potentially leading to sarcopenia, when using glucagon-like peptide-1 (GLP-1)-based therapies, is currently a matter of debate. While most available results are rather reassuring in the general population, sarcopenia may become a concern in some special subgroups with comorbidities known to be associated with a higher risk of sarcopenia, independently of any GLP-1-based therapy.

An extensive literature search was done to identify studies that investigated the effects of GLP-1-based therapies on changes in SMM and sarcopenia in special populations, i.e. older people, patients with type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, and metabolic dysfunction-associated liver disease.

Several publications emphasized the risk of sarcopenia and recommended caution when prescribing GLP-1-based therapies in people with these comorbidities of interest. However, hard data remain scarce in the literature, without any evidence-based demonstration of a significantly increased risk of sarcopenia. Nevertheless, as old age potentiates the risk of sarcopenia, older patients with these comorbidities (especially advanced heart failure or renal disease) deserve more careful attention.

While the risk of sarcopenia associated with GLP-1-based therapies remains controversial in the general population, a higher risk in special populations with comorbidities has been repeatedly emphasized despite the lack of evidence-based data in the literature. Because these agents showed major clinical benefits in patients with such comorbidities but sarcopenia could mitigate them, there is an urgent need to implement dedicated studies with appropriate measures of sarcopenia in these special populations.