First dual GCG/GLP-1ra gains approval from China’s NMPA for chronic weight management

China's National Medical Products Administration (NMPA) has approved Innovent Biologics’ mazdutide, a first-in-class dual glucagon (GCG)/glucagon-like peptide-1 (GLP-1) receptor agonist, for chronic weight management in Chinese adults with overweight or obesity. According to the company, Mazdutide is the world's first dual GCG/GLP-1 receptor agonist approved for weight loss, offering a unique mechanism that enhances weight-loss efficacy while reducing visceral fat and delivering comprehensive metabolic benefits.

As the first marketed dual GCG/GLP-1 receptor agonist, mazdutide has been recommended by multiple clinical guidelines in China and expert consensus on obesity management on account of its innovative mechanism and solid evidence base.

GCG receptors are mainly expressed in the liver, and GCG receptor agonism can inhibit hepatic fat synthesis and promote hepatic lipolysis. As a dual GCG/GLP-1 receptor agonist weight loss drug, mazdutide can deliver significant weight loss efficacy and metabolic benefits such as waist circumstance and liver fat content reductions to adults with overweight or obesity.

The approval of mazdutide was mainly based on data from GLORY-1, a Phase 3 pivotal clinical study conducted in Chinese adults with overweight or obesity. The primary endpoint and all key secondary endpoints of the study were successfully achieved in 2024. Results showed that at weeks 32 and 48, the percentage of body weight reduction from baseline and the proportions of participants with a body weight reduction of ≥5，≥10% and ≥15% in the mazdutide 4 mg group and mazdutide 6 mg group were superior to those of the placebo group.

Based on the efficacy estimand, at week 48, the mean percentage changes in body weight relative to baseline in the mazdutide 4 mg, mazdutide 6 mg, and placebo groups were −12.0%, −14.8%, and −0.5%, respectively.

The proportion of participants with a body weight reduction ≥ 5% relative to baseline were 73.5%, 82.8%, and 11.5%, respectively; the proportion of participants with a body weight reduction ≥ 15% relative to baseline were 37.0%, 50.6%, and 2.1%, respectively. The mean changes in waist circumference relative to baseline were −9.5 cm, −11.0 cm, and −1.5 cm, respectively.

In addition, mazdutide reduced liver fat content in adults with overweight or obesity. Among participants with baseline liver fat content ≥ 10%, the mean percent change from baseline in liver fat content to week 48 were −65.85%, −80.24%, and −5.27% in the mazdutide 4 mg, 6 mg, and placebo groups, respectively.