1866-LB: A Phase 2 Study of Mazdutide 9 mg in Chinese Adults with BMI of 30 kg/m² or more

Introduction & Objective: To evaluate the efficacy and safety of 9 mg mazdutide, a once-weekly GLP-1 and glucagon receptor dual agonist, in Chinese participants with obesity.

Methods: In a randomized, double-blind, placebo-controlled phase 2 trial (NCT04904913), 80 Chinese adults with a BMI of 30 kg/m² or more (mean baseline body weight: 96.9 kg; mean baseline BMI: 34.3 kg/m²) were randomized to receive once-weekly, subcutaneous mazdutide 9 mg (n=60) or placebo (n=20) for 24 weeks. Subsequently, participants voluntarily chose to participate in an extended 24-week double-blind treatment period. The primary endpoint was the percentage change in weight from baseline at week 24.

Results: At week 24, mean percentage change in weight from baseline were −13.3% (SE 0.8) with mazdutide 9 mg and 2.1% (1.5) with placebo (estimated treatment difference: −15.4% [95%CI: −18.8, −12.0], P <0.0001); 81.7%, 65.0% and 31.7% of participants with mazdutide achieved weight reduction of 5% or more, 10% or more, and 15% or more, respectively, while no participant with placebo achieved weight reduction of 5% or more. Furthermore, compared with placebo, greater improvements were observed with mazdutide at week 24 in multiple cardiometabolic risk factors, most notably in triglycerides (−43.5% with mazdutide, −1.7% with placebo), alanine aminotransferase (−32.8%, 12.7%) and serum uric acid (−102.2 µmol/L, −16.1 µmol/L). In participants with baseline liver fat content (as measured by MRI-PDFF) of 5% or more, the liver fat content was reduced by 73.3% after 24-week treatment of mazdutide. Mazdutide 9 mg was well tolerated, with no adverse event leading to treatment discontinuation reported. The most frequently reported adverse events were gastrointestinal, and most were mild to moderate in severity.

Conclusion: In Chinese adults with a BMI of 30 kg/m² or more, mazdutide 9 mg showed robust body weight reduction and prominent hepatic benefits.