Introduction
obesity, metabolic liver diseases, overweight, metabolic disorders, weight loss
OBESITY, TYPE 2 DIABETES, METABOLIC DISORDERS
After rapidly growing prevalence over the past four decades, overweight and obesity now affect more than half of adult population in ChinaMultiple lines of evidence suggest that a body weight reduction of 5–15% could significantly improve metabolic disorders and reduce the risk for type 2 diabetes, cardiovascular diseases, metabolic liver diseases and other weight-related comorbiditiesIn 2021, the US FDA approved once-weekly semaglutide 2.4 mg for long-term body weight managementMazdutide (also known as IBI362 or LY3305677), a mammalian oxyntomodulin analogue with a fatty acid side chain attached, is being developed as a once-weekly GLP-1 and glucagon receptor dual agonist for the treatment of obesity and type 2 diabetes. In a phase 1b clinical trial in Chinese overweight adults or adults with obesity, mazdutide dosed up 10 mg was well tolerated, with overall safety profiles similar to those of other GLP-1 receptor agonists and co-agonistsHere, in a randomised, double-blind, placebo-controlled phase 2 trial, we further assess the efficacy and safety of mazdutide in Chinese overweight adults or adults with obesity. Mazdutide demonstrates robust and clinically meaningful body weight loss after 24 weeks of treatment, together with improvements on multiple cardio-metabolic risk factors. Mazdutide is well tolerated up to 6 mg over 24 weeks, with safety profile consistent with those observed in previous studies.