Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled phase 2 trial
OBJECTIVE We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of mazdutide, a once-weekly GLP-1 and glucagon receptor dual agonist, in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Adults with type 2 diabetes inadequately controlled with diet and exercise alone or with stable metformin (glycated haemoglobin A1c [HbA1c] of 7.0%–10.5% [53–91 mmol/mol]) were randomized to receive mazdutide 3 mg (n = 51), mazdutide 4.5 mg (n = 49), mazdutide 6 mg (n = 49), open-label dulaglutide 1.5 mg (n = 50) or placebo (n = 51) subcutaneously for 20 weeks. The primary outcome was change from baseline to week 20 in HbA1c. RESULTS Mean changes in HbA1c from baseline to week 20 ranged from −1.41% to −1.67% with mazdutide (−1.35% with dulaglutide and 0.03% with placebo) (all p<0.0001 versus placebo). Mean percent changes in body weight from baseline to week 20 were dose-dependent and up to −7.1% with mazdutide (−2.7% with dulaglutide and −1.4% with placebo). At week 20, participants with mazdutide were more likely to achieve HbA1c target of <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol), and body weight loss from baseline of ≥5% and ≥10%, compared with placebo-treated. The most common adverse events with mazdutide included diarrhoea (36%), decreased appetite (29%), nausea (23%), vomiting (14%) and hypoglycemia (10%; 8% with placebo). CONCLUSIONS In Chinese patients with type 2 diabetes, mazdutide dosed up to 6 mg was generally safe and demonstrated clinically meaningful HbA1c and body weight reduction. Article Highlights l Despite increasing application of GLP-1 receptor agonists in glycemic control, evidence of co-agonism with glucagon receptor in the treatment of type 2 diabetes remains limited. l Does mazdutide, a once-weekly GLP-1 and glucagon receptor dual agonist, reduce HbA1c and body weight in patients with type 2 diabetes? l In this phase 2 study, 20 weeks’ treatment with mazdutide achieved mean HbA1c reductions up to 1.67% and mean body weight reductions up to 7.1%. The most common adverse events with mazdutide were gastrointestinal in nature. l The results supported future development of mazdutide for the treatment of type 2 diabetes.