Innovent Biologics reported that mazdutide 9 mg, a potential first-in-class dual GCG/GLP-1 receptor agonist, achieved up to 20.1% weight loss in Chinese adults with obesity in the Phase 3 GLORY-2 trial, meeting its primary endpoint and all key secondary endpoints. Innovent is developing mazdutide for China under a 2022 license from Eli Lilly & Co.
GLORY-2 enrolled 462 adults with obesity, including 16% with type 2 diabetes, in a 2:1 randomization of mazdutide 9 mg vs placebo. Participants receiving mazdutide experienced continuous weight loss through Week 60 with no plateau, achieving an 18.55% mean weight reduction (3.02% for placebo). A total of 44.0% achieved ≥20% weight loss (vs 2.6% for placebo).
In participants without type 2 diabetes, mean weight loss reached 20.08%, with 48.7% achieving ≥20% weight loss.
Mazdutide improved all cardiometabolic secondary endpoints, including waist circumference, systolic blood pressure, triglycerides, non-HDL-C, LDL-C, and uric acid. A liver-fat substudy showed a 71.9% reduction in participants with elevated baseline liver fat (placebo: +5.1%). The drug was well tolerated, with only 2.9% discontinuing treatment.
Positioning as a non-surgical option
Investigators highlighted the implications for patients with moderate-to-severe obesity in China, who are often candidates for metabolic surgery. Prof. Linong Ji (Peking University People’s Hospital) said the treatment could support “stratified weight management” and broaden non-surgical choices. Innovent’s Chief R&D Officer Lei Qian noted that mazdutide is the only GLP-1-based therapy in China to deliver >20% weight loss in adults without diabetes with a one-year regimen. Innovent plans to file an NDA for the new indication with the NMPA in the near term.
Innovent’s late-stage program for mazdutide
Mazdutide, originally in-licensed from Lilly, secured its first global approval in China earlier this year for chronic weight management and glycemic control in type 2 diabetes. Innovent has completed seven Phase 3 trials in obesity and diabetes, with five meeting primary endpoints, including comparisons against semaglutide.
In DREAMS-3, mazdutide outperformed semaglutide in both glycemic control and weight loss, with 48% of participants achieving HbA1c <7.0% and ≥10% weight loss, compared with 21% for semaglutide. Innovent also plans a head-to-head study against Lilly’s tirzepatide (Mounjaro).
The GCG/GLP-1 dual-agonist rationale
Dual agonism of the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R) is being explored as a therapeutic strategy for obesity and type 2 diabetes due to the complementary metabolic actions of these hormones.
GLP-1 analogs are established for diabetes and obesity treatment, improving glycemic control, reducing appetite, and promoting weight loss through enhanced insulin secretion and delayed gastric emptying. Meanwhile, glucagon increases energy expenditure and promotes lipolysis, but also raises blood glucose. When combined with GLP-1 agonism, the hyperglycemic effect of glucagon can be counterbalanced, allowing the energy-expending benefits without worsening glycemia.
The promise is that dual GCGR/GLP-1R agonists may offer greater efficacy for weight loss and metabolic improvement than GLP-1R agonists alone, with Innovent’s data readouts for mazdutide appearing to back up evidence generated in preclinical studies (see examples here, here, and here). Eli Lilly is hoping to confirm Innovent’s data for mazdutide in several ongoing multiregional trials, with Phase 2 the latest stage of development outside China.