Mazdutide: An emerging glucagon/GCG-like peptide-1 dual receptor agonist for obesity—a comparison of therapeutic effects and potential side effects with GCG-like peptide-1 inhibitors

Obesity has emerged as a global health crisis, necessitating effective therapeutic options. The “GLORY-1” study evaluated the efficacy and safety of mazdutide, a dual receptor agonist targeting glucagon (GCG) and GCG-like peptide-1 (GLP-1). As the first GLP-1/GCG dual-receptor agonist to successfully complete phase 3 trials, this drug marks a significant advancement in innovative drug discovery for endocrine and metabolic diseases in China. Unlike conventional GLP-1 receptor (GLP-1R) single-target drugs, mazdutide activates both GCG receptor (GCGR) and GLP-1R simultaneously, enhancing fat oxidation and offering substantial benefits for weight reduction and comprehensive metabolic regulation. In terms of safety, mazdutide exhibits an overall safety profile comparable to existing GLP-1R agonists, with adverse events primarily involving mild to moderate gastrointestinal disturbances. Notably, GLP-1R inhibitors exhibit significantly fewer side effects than agonists, suggesting potential for long-term safety in mazdutide combination therapies. In conclusion, the GLORY-1 study underscores mazdutide’s promise as an effective obesity treatment. This review systematically investigates the therapeutic potential of mazdutide by examining its pharmacological mechanisms, clinical trial design, and safety considerations. Furthermore, it offers an initial evaluation of the prospects for combining mazdutide with GLP-1R inhibitors. These insights present new avenues for personalized obesity treatment and aim to enhance its clinical application.