The synergistic potential of GLP-1R agonist dulaglutide and ghrelin receptor analogue anamorelin in ameliorating muscle atrophy

Abstract

Muscle atrophy represents a multifaceted and intricate syndrome characterized by the reduction in both mass and strength of skeletal muscles, leading to muscle dysfunction and weakness. Its potential causes encompass aging, denervation, disuse, and various diseases. One well-known pharmacological agent for glycemic control in diabetes patients is the glucagon-like peptide-1 receptor (GLP-1R) agonist. Our recent research findings have shown that compounds such as exendin-4 (Ex-4) or dulaglutide can effectively mitigate muscle atrophy in dexamethasone (Dex)-induced cellular and animal models as well as chronic kidney disease (CKD) and rodent sarcopenia models. However, it’s noteworthy that these agents may concurrently induce a decrease in body weight following administration, posing challenges when considering them as potential treatments for muscle atrophy in cachectic and sarcopenic conditions. Ghrelin, being the sole circulating orexigenic hormone known to be associated with growth hormone release, offers a potential solution to counterbalance the appetite-inhibiting effect of GLP-1R agonists. Additionally, ghrelin enhanced muscle anabolism and exerted protective effects for muscle atrophy. Therefore, combination of a GLP-1R agonist and a ghrelin analogue emerges as a synergistic therapeutic approach to effectively combat muscle atrophy.