GLP-1 receptor agonists and sarcopenia: Weight loss at a cost? A brief narrative review

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual agonists targeting both GLP-1 and glucose-dependent insulinotropic polypeptide receptors (GLP-1/GIP RAs) are established therapies for type 2 diabetes mellitus (T2DM) and obesity. However, there is evidence that treatment with these agents may lead to significant loss of muscle mass, potentially resulting in sarcopenia or sarcopenic obesity. This brief narrative review explores the complex relationship between GLP-1 based therapies and muscle health. Some studies have linked GLP-1 RAs and dual GLP-1/GIP RAs with significant reductions in lean mass, and sarcopenia. However, preclinical evidence suggests that these agents can attenuate skeletal muscle atrophy, improve muscle function, and enhance mitochondrial health. Moreover, limited clinical data indicate a potential role in preserving muscle mass under certain conditions. Management includes optimised diet, targeted exercise, and novel pharmacological interventions, such as blockade of growth differentiation factor-8 (GDF8) and activin A (ActA). These measures hold potential to preserve muscle mass and to improve patient outcomes. Further research is warranted to clarify these mechanisms and to evaluate combination therapies aimed at preventing sarcopenia in patients receiving GLP-1 RAs.

Keywords: GLP-1 RAs; GLP-1/GIP RAs; Sarcopenia; T2DM; Weight loss.