Chinese Original Weight Loss Drug Featured in NEJM: Comparable Efficacy to Semaglutide with Lower Discontinuation Due to Side Effects

In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists represented by semaglutide have demonstrated powerful weight loss effects and continue to be hot sellers worldwide. Tirzepatide, a dual agonist of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, has also shown strong weight loss efficacy.

Mazdutide is a GLP-1 class drug independently developed by Innovent Biologics. Unlike semaglutide and tirzepatide, Mazdutide targets the GLP-1 receptor and glucagon (GCG) receptor. Activation of the GLP-1 receptor suppresses appetite and delays gastric emptying, thereby reducing food intake; activation of the GCG receptor promotes liver fat breakdown and enhances energy expenditure, improving fatty liver. This dual mechanism not only synergistically promotes weight loss but also directly improves hepatic fat metabolism, alleviating obesity-related fatty liver issues.

On May 24, 2025, the internationally renowned medical journal The New England Journal of Medicine (NEJM) published the results of the phase 3, double-blind, placebo-controlled clinical trial GLORY-1 led by Professor Linong Ji from Peking University People’s Hospital on the GLP-1 weight loss drug Mazdutide.

The paper titled “Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight” lists Professor Linong Ji from Peking University People’s Hospital and Professor Hongwei Jiang from the First Affiliated Hospital of Henan University of Science and Technology as co-first authors; Professor Ji and Dr. Lei Qian from Innovent Biologics are co-corresponding authors.

This phase 3 clinical trial showed that in Chinese adults with obesity or overweight, once-weekly injections of Mazdutide demonstrated good weight loss efficacy and safety.

It is reported that this is the world’s first and only clinical study of a GLP-1/GCG receptor dual agonist submitted for market approval published in a top medical journal. This will rewrite clinical treatment and guidelines for overweight and obesity diseases domestically and internationally. It is also the first time that innovative drug clinical research results in China’s metabolic and endocrine disease field have appeared in NEJM, marking a new level in China’s drug R&D and biotechnology innovation.

Notably, Innovent Biologics is conducting clinical trials of Mazdutide for obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatohepatitis (MASH).

In this China-based phase 3, double-blind, placebo-controlled clinical trial, adults aged 18–75 with a body mass index (BMI) ≥ 28, or BMI between 24–28 with at least one weight-related comorbidity, were randomized 1:1:1 to receive 4 mg Mazdutide, 6 mg Mazdutide, or placebo for 48 weeks. The two primary endpoints were percentage change in body weight from baseline and the proportion of participants achieving at least 5% weight loss at week 32.

Among 610 participants, the average baseline weight was 87.2 kg with a mean BMI of 31.1. At week 32, the mean weight change percentages were -10.09%, -12.55%, and 0.45% in the 4 mg, 6 mg, and placebo groups respectively. The proportions of participants who lost at least 5% of their weight were 73.9%, 82.0%, and 10.5% respectively.

At week 48, the mean weight change percentages were -11.00%, -14.01%, and 0.30% in the 4 mg, 6 mg, and placebo groups respectively. The proportions achieving at least 15% weight loss were 35.7%, 49.5%, and 2.0% respectively.

Beyond effective weight loss, Mazdutide showed beneficial effects on all pre-specified cardiovascular metabolic markers.

These results indicate that participants in both the 4 mg and 6 mg Mazdutide treatment groups achieved clinically significant weight loss.

Regarding safety, the most commonly reported adverse events were gastrointestinal-related, mostly mild to moderate and occurring mainly early in treatment. The rates of adverse events causing trial discontinuation were 1.5% for the 4 mg group, 0.5% for the 6 mg group, and 1.0% for placebo. The probability of discontinuation due to side effects was significantly lower than that reported for semaglutide and tirzepatide.

Key Highlights

• High weight loss efficacy: The 6 mg treatment group achieved an average weight loss of 12.55% (~11 kg) at 32 weeks and 14.01% (~12 kg) at 48 weeks; 49.5% of participants lost over 15% of their weight (equivalent to going from about 180 lbs to 150 lbs).
• Metabolic improvements: The 6 mg group showed a 10.7 cm waist circumference reduction (about 2-3 pants sizes smaller), 8.5 mmHg reduction in systolic blood pressure, 36.7 μmol/L decrease in uric acid, 29% reduction in triglycerides, and significant improvement in fatty liver.
• High safety profile: Main side effects were nausea and diarrhea, mostly mild to moderate and concentrated early in treatment. The 6 mg group had a very low discontinuation rate of 0.5%, significantly lower than semaglutide, tirzepatide, and similar drugs.

Overall, this study confirms the efficacy and safety of Mazdutide, the world’s first GLP-1/GCG receptor dual agonist submitted for market approval, in managing overweight and obesity. It marks a new milestone for China’s independently developed innovative weight loss drugs entering the international forefront of clinical research.

Reference

[1].Linong Ji, M.D.1 https://orcid.org/0000-0002-3262-2168, Hongwei Jiang, M.D.2, Yan Bi, M.D.3, Hua Li, M.D.4, Junhang Tian, M.D.5, Dexue Liu, M.D.6, Yuzhu Zhao, M.D.7, Wei Qiu, M.D.8, Chongbing Huang, M.D.9, Lei Chen, M.D.10, Shao Zhong, M.D.11, Jie Han, M.D.12, Yawei Zhang, M.D.13, Qiufang Lian, M.D.14, Ping Yang, M.D.15, Lingchun Lv, M.D.16, Jieyu Gu, M.D.17, Zihan Liu, M.D.17, Huan Deng, M.D.17, Yanqi Wang, M.Sc.17, Li Li, Ph.D.17, Lijuan Pei, Ph.D.17, and Lei Qian, M.D.17, for the GLORY-1 Investigators. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. url:https://www.nejm.org/doi/full/10.1056/NEJMoa2411528