Wen Jimmy, Ansari Ubaid, Shehabat Mouhamad, Ansari Zaid, Syed Burhaan, Razick Adam, Razick Daniel, Akhtar Muzammil, Frezza Eldo
California Northstate University College of Medicine, Elk Grove, California, USA.
University of California, Los Angeles, Los Angeles, California, USA.
J Diabetes. 2025 Aug;17(8):e70119. doi: 10.1111/1753-0407.70119.
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.
胰高血糖素样肽-1受体激动剂（GLP-1 RAs）已在糖尿病和肥胖患者中显示出显著的减重效果。然而，鉴于其诱导的快速体重减轻，人们担心身体成分的总体变化，包括去脂体重（LBM）。目前关于这些影响的文献存在显著异质性，一些研究报告LBM减少40%-60%，而其他研究报告减少15%或更少。为了解决这个问题，选择性雄激素受体调节剂（SARMs）已成为热门候选药物。鉴于其对雄激素受体的选择性，SARMs具有显著的合成代谢特性，并且与传统合成代谢化合物相比，其安全性有所改善。其中几种药物，如恩杂鲁胺，已在涉及老年患者群体或患有慢性疾病继发恶病质或肌肉减少症的患者的临床试验中进行了研究。此外，其他用于维持或增加LBM的药物，如抗肌生成抑制素药物，也在研究中。探索这种潜在的协同作用可能会使使用GLP-1 RAs进行糖尿病或减重治疗的患者实现更好的体重减轻和身体成分管理。本综述旨在评估SARMs在改善GLP-1 RAs引起的身体成分变化方面的潜在益处和用途。还将讨论其他用于保留或增加肌肉量的研究药物以及这些药物未来的可能性。
