July 09, 2025
3 min read
Key takeaways:
- Mazdutide lowered body weight and improved multiple cardiometabolic markers in adults with obesity.
- Gastrointestinal adverse events were most common with the drug and were mostly mild to moderate.
A GLP-1/glucagon dual agonist conferred weight loss of up to 12.55% at 32 weeks for adults with overweight or obesity, according to data from a phase 3 trial conducted in China.
As Healio previously reported, findings from the phase 3 DREAMS-2 trial revealed mazdutide (Eli Lilly/Innovent) conferred greater reductions in HbA1c and body weight than dulaglutide (Trulicity, Eli Lilly) among adults with type 2 diabetes. Data from the GLORY-1 trial published in The New England Journal of Medicine showed 4 mg or 6 mg doses of the novel once-weekly dual agonist induced a 5% or greater weight loss at 32 weeks among most participants.
“The results also showed improvements in multiple metabolic indicators, which are expected to reduce the incidence of obesity-related complications and alleviate associated health care burden,” Linong Ji, MD, professor of medicine in the department of endocrinology and metabolism at Peking University People’s Hospital in China, told Healio. “These results, together with the overall favorable tolerability and safety profiles, provide important clinical evidence on the applicability of GLP-1s in Chinese adults with overweight or obesity, and support the use of mazdutide as a new treatment option for weight management in the Chinese population.”
Linong Ji
The GLORY-1 trial enrolled 610 adults aged 18 to 75 years with obesity or overweight plus one weight-related comorbidity (mean age, 34.2 years). Obesity was defined according to Chinese criteria, with overweight defined as a BMI of 24 kg/m2 to 27.9 kg/m2 and obesity as a BMI of 28 kg/m2 or higher. Participants were randomly assigned to once-weekly subcutaneous 4 mg mazdutide, 6 mg mazdutide or placebo for 48 weeks, followed by a 12-week off-treatment follow-up. The primary endpoints were percentage change in body weight from baseline to 32 weeks and percentage of participants with a weight loss of 5% or more at 32 weeks.
Weight change
The 4 mg mazdutide group had a 10.09% decline in body weight and those receiving 6 mg mazdutide had a mean weight loss of 12.55% from baseline to 32 weeks compared with a 0.45% weight gain for the placebo group (P < .001 for both). A weight loss of 5% or more was achieved by 73.9% of adults receiving 4 mg mazdutide, 82% of those receiving 6 mg mazdutide and 10.5% of the placebo group (P < .001 for both).
At 48 weeks, the 4 mg mazdutide group lost a mean 11% of body weight and the 6 mg dose cohort achieved a 14.01% weight loss vs. a 0.3% weight gain for the placebo group (P < .001 for both). A 15% or greater decrease in body weight was reached by 35.7% of the 4 mg mazdutide group and 49.5% of the 6 mg group vs. 2% of the placebo group at 48 weeks (P < .001 for both).
Cardiometabolic measures
Decrease in waist circumference at 48 weeks was 9.12 cm with 4 mg mazdutide and 10.72 cm with 6 mg mazdutide vs. a 1.41 cm reduction with placebo (P < .001 for both). Both mazdutide groups pooled together also had greater improvements in systolic blood pressure (mean change, –8.56 mm Hg vs. –2.13 mm Hg), triglycerides (mean change, –58 mg/dL vs. –14 mg/dL), total cholesterol (mean change, –11 mg/dL vs. 6 mg/dL), LDL cholesterol (mean change, –8 mg/dL vs. 4 mg/dL), serum uric acid (mean change, –0.6 mg/dL vs. 0.1 mg/dL) and alanine aminotransferase (mean change, –13.92 U/L vs. –4.44 U/L) than the placebo group (P < .001 for all).
“[There were] rapid improvements in multiple metabolic indicators, especially in reductions of serum uric acid levels and liver fat content, which might be attributable to glucagon-driven lipid oxidation in the liver and in adipose tissue, highlighting mazdutide’s comprehensive regulation of systemic metabolism,” Ji said.
Safety data
Three adults receiving 4 mg mazdutide, one receiving 6 mg mazdutide and two in the placebo group discontinued the trial due to adverse events. The most frequently reported adverse events were nausea, diarrhea and vomiting. Most were mild or moderate in severity and were most common during dose escalation.
Heart rate increases were observed in both mazdutide groups. Heart rate peaked during dose escalation and later declined during the dose maintenance phase of the study.
Sinus tachycardia occurred in 2% of adults receiving 4 mg mazdutide, 4.5% of those receiving 6 mg mazdutide and 2.9% of adults receiving placebo.
Ji said more studies are ongoing to assess mazdutide for adolescents with obesity, those with obesity and metabolic dysfunction-associated fatty liver disease, and adults with obesity plus obstructive sleep apnea. He added that research is also being conducted to evaluate the impact of higher doses of mazdutide.
“A long-term study needs to be conducted to evaluate the sustained weight-loss effect of mazdutide,” Ji said.
For more information:
Linong Ji, MD, can be reached at jiln@bjmu.edu.cn.