1225-OR: Efficacy and Safety of Mazdutide 9 mg in Chinese Adults with Obesity: Results from the Phase 3 GLORY-2 Trial

Introduction and Objective: To evaluate the efficacy and safety of mazdutide (MAZ) 9 mg, a once-weekly GLP-1 and glucagon receptor dual agonist, in Chinese adults with obesity. Methods: In this randomized, double-blind, placebo (PBO)-controlled trial (NCT06164873, GLORY-2), 462 Chinese adults with obesity (BMI ≥30 kg/m2; 16.0% with T2D) were randomized in a 2:1 ratio to receive once-weekly, subcutaneous MAZ 9 mg or PBO for 60 weeks. Co-primary endpoints were the percentage change in weight from baseline and a weight reduction (WR) of ≥5% at week 60. Results: At baseline, the mean body weight was 94.0 kg and the mean BMI was 34.3 kg/m2. MAZ 9 mg met both co-primary endpoints and all key secondary endpoints. At week 60, the percentage change in body weight from baseline was-18.5 % with MAZ 9 mg, -3.0 % with PBO (treatment difference: -15.5% 95% CI:-17.6, -13.4); 85.7% of participants with MAZ 9 mg, 33.2% with PBO achieved a WR of ≥5%; 44.0% of participants with MAZ 9 mg, 2.6% with PBO achieved a WR of ≥20%. For participants without T2D, the percentage change in body weight from baseline was -20.1 % with MAZ 9 mg, -2.8 % with PBO at week 60 (treatment difference: -17.3% -19.6, -15.0); 88.2% of participants with MAZ 9 mg, 32.3% with PBO achieved a WR of ≥5%; 48.7% of participants with MAZ 9 mg, 3.1% with PBO achieved a WR of ≥20% (P0.001 for all comparisons). MAZ 9 mg also demonstrated significant improvements in blood pressure, lipids, and serum uric acid levels. MAZ was well tolerated, with AEs leading to treatment discontinuation reported in 2.9% of participants with MAZ 9 mg, and 0% with PBO. The most common AEs were gastrointestinal, mostly mild to moderate in severity. Conclusion: In Chinese adults with obesity, MAZ 9 mg provides clinically significant and superior weight loss compared with PBO, along with improvements in cardiometabolic risk factors and a favourable safety profile. Disclosure L. Ji: None. L. Gao: Consultant; Current; Innovent Biologics, Inc. H. Jiang: Consultant; Current; Innovent Biologics. H. Cai: None. J. Tian: None. B. Shi: None. W. Qiu: None. Y. Wang: Employee; Current; Innovent Biologics, Inc. L. Li: Employee; Current; Innovent Biologics, Inc. Q. Ma: Employee; Current; Innovent Biologics. H. Deng: Employee; Current; Innovent Biologics, Inc. L. Pei: Employee; Current; Innovent Biologics, Inc. H. Han-Zhang: None. L. Qian: Employee; Current; Innovent Biologics, Inc. Funding Innovent Biologics, Inc.