Mazdutide in Asian Obesity: Mechanistic Rationale, Emerging Clinical Evidence, and Relevance to South Asia

A bstract Obesity in Asian populations is characterized by a distinctive metabolic phenotype, with insulin resistance, visceral adiposity, metabolic dysfunction-associated steatotic liver disease, and type 2 diabetes often developing at lower body mass index thresholds than in White populations, highlighting the need for population-specific therapeutic evidence. In this context, STEP-7 and GLORY-1 provide important East Asian data on semaglutide 2.4 mg and mazdutide, respectively. Semaglutide acts through selective glucagon-like peptide-1 (GLP-1) receptor agonism, whereas mazdutide combines GLP-1 and glucagon receptor agonism, providing a mechanistic rationale for effects beyond appetite suppression alone. In STEP-7, semaglutide was associated with a mean body-weight reduction of 12.1% at 44 weeks, whereas GLORY-1 demonstrated dose-dependent weight loss with mazdutide, with reductions of 11.0% at 4 mg and 14.01% at 6 mg over 48 weeks. GLORY-1 also reported marked reductions in liver fat, suggesting potential relevance in patients with obesity complicated by hepatic steatosis or broader metabolic dysfunction. Emerging data from DREAMS-3 and the GLORY program are promising, but whether mazdutide can translate its early efficacy into durable cardiovascular, renal, and metabolic benefits beyond those of GLP-1 receptor agonists remains to be established.