Dual GCG/GLP-1 Agonist Mazdutide 9 mg Produces 20% Weight Loss in Phase 3 Trial of Chinese Adults with Obesity

The phase 3 GLORY-2 clinical trial found that mazdutide 9 mg produced a mean weight reduction of 18.55% at 60 weeks in Chinese adults with obesity, with nearly half of participants without type 2 diabetes (T2D) achieving at least 20% weight loss. In an annoucement this morning, Innovent Biologics reported that the study met its primary endpoints and all key secondary endpoints, prompting the company to share plans to submit a new drug application to China's National Medical Products Administration (NMPA).

Mazdutide is a first-in-class dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist being codeveloped with Eli Lilly, according to Innovent. In addition to the effects of the GLP-1 RA activity, ie, lowering blood glucose and reducing body weight, mazdutide may also increase energy expenditure and improve hepatic fat metabolism through glucagon receptor activation, the company said.

Chinese Obesity Epidemic

The number of individuals with obesity in China tripled between 2004 and 2018, according to a recent analysis, and by 2014 the country had the greatest number of adults with obesity in the world, at 90 billion. The combined prevalence of overwieght and obesity in the adult Chinese population exceeded 50% by 2020.2

"This patient population requires special attention in clinical weight management and metabolic syndrome prevention," professor Linong Ji, the study's principal investigator at Peking University People's Hospital, said in a statement. "According to current Chinese clinical guidelines, metabolic surgery is often considered a first-line treatment for such patients. Extensive clinical evidence on GLP-1 receptor agonists demonstrates that the weight-loss efficacy of these drugs is dose-dependent. Therefore, developing pharmacological treatments tailored to moderate-to-severe obesity could offer new therapeutic options for this group," he stressed.

The Phase 3 GLORY-2 Trial

The randomized, double-blind trial enrolled 462 participants with a body mass index (BMI) of 30 kg/m² or greater, including 16% with T2D. Researchers randomly assigend participants in a 2:1 ratio to receive either mazdutide 9 mg or placebo, combined with lifestyle intervention, over 60 weeks. The cohort had a mean baseline weight of 94.0 kg, and mean BMI was 34.3 kg/m².

Investigators reported continuous weight loss through week 60 among participants in the mazdutide group, with no plateau observed. Mean weight reduction in the placebo group was 3.02% over the same period. Among all participants, 44.0% in the mazdutide 9 mg group achieved weight reduction of 20% or more, compared with 2.6% in the placebo group (P <.001).

Weight Loss in Those Without T2D

The secondary endpoints showed even more pronounced effects in participants without T2D. This subgroup achieved a mean weight reduction of 20.08% at week 60 with mazdutide 9 mg, compared with 2.81% for placebo. Among these participants, 48.7% achieved at least 20% weight reduction, versus 3.1% in the placebo group (P <.001).

According to Innovent, GLORY-2 met all key secondary endpoints, including improvements in waist circumference, systolic blood pressure, triglycerides, non-HDL cholesterol, LDL cholesterol, and serum uric acid levels. Mazdutide 9 mg demonstrated superiority to placebo across all weight-loss and cardiometabolic endpoints.

The study also evaluated liver fat content in a subgroup of participants, using magnetic resonance imaging-proton density fat fraction. Among those without T2D whose baseline liver fat content was 10% or greater, the mean percent change in liver fat content from baseline to week 60 was -71.9% in the mazdutide 9 mg group compared with 5.1% in the placebo group.

Tolerability and safety profiles were both favorable, according to the Innovent statement, with no new safety signals. Gastrointestinal adverse events, an expected feature of incretin-mimetic therapy, were mild to moderate in severity and transient. The proportion of participants who discontinued treatment prematurely due to adverse events was 2.9% in the mazdutide 9 mg group and 0% in the placebo group.

Hope for the Future

"China faces a high prevalence of obesity, with obese individuals bearing a significant burden of cardiometabolic diseases. Those with a BMI exceeding 32.5 kg/m² often experience an even greater cardiometabolic burden," professor Ji said.

"Mazdutide 9 mg is currently the only GLP-1 receptor agonist that achieves over 20% weight loss in obese adults without T2D after 1 year of treatment with just a 2-step dose titration," Lei Qian, Innovent chief R&D officer of general biomedicine, added.

China's China’s National Medical Products Administration has already approved mazdutide for 2 indications: chronic weight management in adults with BMI 28 kg/m² or greater or BMI of 24 kg/m² or greater with weight-related comorbidities, and for glycemic control in adults with T2D as monotherapy or in combination with other agents.

Innovent has conducted or completed 7 phase 3 clinical studies of mazdutide, with the first 5 meeting their primary endpoints. The company continues to investigate the drug in additional populations, including adolescents with obesity and patients with metabolic dysfunction-associated steatohepatitis and heart failure with preserved ejection fraction, the company said.

References

1. Mazdutide 9 mg achieves up to 20.1% weight loss in Chinese adults wtih obeisty, GLORY-2 study meets primary and all key secondary endpoints. News release. Innovent Biologics. November 20, 2025. Accessed November 20, 2025. https://en.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=562
2. Zhang G, Zhang H, Liu GG, Shi L. Obesity and occupational disparities in urban China: evidence from a large-scale cross-sectional study. Healthcare (Basel). 2025;13(17):2225. doi: 10.3390/healthcare13172225