The Potential of SARMs and Antimyostatin Agents in Addressing Lean Body Mass Loss From GLP-1 Agonists: A Literature Review

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated substantial weight loss effects among patients with diabetes and obesity. However, given the rapid weight loss induced, there is concern about the total change in body composition, including lean body mass (LBM). Current literature on these effects contains significant heterogeneity, with some studies reporting a loss of 40%–60% of LBM and others reporting 15% or less. To combat this, selective androgen receptor modulators (SARMs) have become a popular candidate. Given their androgen receptor selectivity, SARMs have notable anabolic properties and proposed improved safety profiles over traditional anabolic compounds. Several of these agents, such as enobosarm, have been investigated in clinical trials involving older patient populations or patients with cachexia or sarcopenia secondary to chronic diseases. Furthermore, other agents to maintain or enhance LBM, such as antimyostatin agents, are also under investigation. Exploring this potential synergy could lead to better weight loss and body composition management in patients using GLP-1 RAs for diabetes or weight loss therapy. This review aims to evaluate the potential benefits and uses of SARMs in ameliorating the body composition changes induced by GLP-1 RAs. Other investigational agents to retain or increase muscle mass and the future possibilities of these drugs will be discussed.