Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight

The GLORY-1 trial was the registrational phase 3, randomized, double-blind, placebo-controlled study evaluating mazdutide, a dual GLP-1 and glucagon receptor agonist developed in China by Innovent Biologics, in Chinese adults with obesity or overweight. 610 participants were randomized with BMI >=28 (obesity) or BMI >=24 with at least one obesity-related comorbidity, into three arms (subcutaneous mazdutide 4 mg, 6 mg, or placebo weekly) over 48 weeks.

The primary endpoints were percentage change in body weight and proportion of patients with >=5% weight loss at 32 weeks:

• Week 32: loss of -10.09% (4 mg) and -12.55% (6 mg) vs. +0.45% with placebo
• 73.9% and 82.0% of patients on mazdutide doses achieved >=5% weight loss vs. 10.5% with placebo
• Week 48: loss of -11.00% (4 mg) and -14.01% (6 mg) vs. +0.30% with placebo
• 49.5% in the 6 mg group achieved >=15% weight loss vs. 2.0% with placebo

Cardiometabolic benefits were broad: significant reductions in waist circumference, blood pressure, lipid profile, glucose, and liver enzymes (ALT). The glucagonergic component of mazdutide — differentiating it from pure GLP-1 agonists — may contribute to greater energy expenditure and favorable hepatic effects. The safety profile was consistent with the class, with transient gastrointestinal events being most common; mean heart rate increase was modest (2.6 bpm) without cardiovascular risk signals.

GLORY-1 was the first NEJM publication of a phase 3 trial of a metabolic therapy developed in China, marking the country's entry into world-class antiobesity drug development. Mazdutide represents a new category — dual GLP-1/glucagon agonists — that may offer complementary benefits to dual GIP/GLP-1 agonists (tirzepatide) and triple agonists (retatrutide) in obesity and associated metabolic diseases.