Mazdutide Demonstrates Superior Glycemic Control and Weight Loss vs Semaglutide in Head-to-Head Trial

Mazdutide, an investigational glucagon-like peptide-1 (GLP-1) and glucagon (GCG) dual receptor agonist, significantly outperformed semaglutide in achieving combined glycemic and weight loss targets in patients with type 2 diabetes (T2D) and obesity, according to results from the first-of-its-kind phase 3 DREAMS-3 trial announced by Innovent Biologics on October 26, 2025.1

The trial met its primary endpoint, with 48.0% of participants in the mazdutide group achieving both HbA1c less than 7% and 10% or more reduction in body weight from baseline at 32 weeks,1,2 compared to 21.0% in the semaglutide group (P <.001). DREAMS-3 represents the world's first phase 3 head-to-head comparison of a GLP-1/glucagon dual receptor agonist against semaglutide in diabetes treatment.1

The Phase 3 DREAMS-3 Trial

Investigators enrolled 349 Chinese adults with early-stage T2D (duration less than 10 years) and obesity whose glycemic and weight control remained inadequate after lifestyle intervention with or without metformin monotherapy.2 Participants had a mean age of 42.4 years, mean baseline HbA1c of 8.02%, mean body weight of 90.47 kg, and mean BMI of 32.98 kg/m².1

Participants were randomly assigned to receive either mazdutide 6 mg or semaglutide 1 mg for 32 weeks in an open-label, multicenter trial. The mazdutide arm then continued into an extension period with different doses for another 24 weeks based on whether participants achieved their weight loss targets.2

Key Efficacy Results

At week 32, mazdutide demonstrated superior efficacy across multiple metabolic parameters. The mean HbA1c reduction from baseline reached -2.03% in the mazdutide group versus -1.84% in the semaglutide group (p<0.05). Mean percentage weight reduction measured 10.29% with mazdutide compared to 6.00% with semaglutide (P <.05).1

"As the world's first approved GCG/GLP-1 dual receptor agonist, mazdutide has demonstrated superior efficacy in glucose lowering and weight loss over semaglutide in the latest phase 3 clinical trial," Professor Linong Ji, principal investigator of DREAMS-3 at Peking University People's Hospital, said in a statement.1 "Mazdutide also provides multiple metabolic benefits and has a favorable safety profile, making it a new-generation GLP-1-based therapy suitable for Chinese patients."1

Safety

The overall safety profile of mazdutide was consistent with previous clinical studies, according to Innovent. Researchers identified no new safety signals. The most common adverse events were gastrointestinal symptoms, with investigators reporting these as mostly mild to moderate in severity.

Clinical Context

Lead investigator Ji emphasized the clinical importance of dual metabolic targets in this patient population. "Among the vast population with T2D in China, the proportion of those with comorbid obesity has been increasing," he noted. "Previous studies have indicated that, compared with non-obese patients with diabetes, patients with T2D and comorbid obesity experience more challenging glycemic control, along with a significant increase in cardiovascular mortality risk and overall cardiovascular disease risk."

Dual Mechanism of Action

Mazdutide functions as a mammalian oxyntomodulin analogue. Beyond the effects of GLP-1 receptor agonists on promoting insulin secretion, lowering blood glucose, and reducing body weight, mazdutide may also increase energy expenditure and improve hepatic fat metabolism through glucagon receptor activation. Clinical studies have shown the agent reduces waist circumference, blood lipids, blood pressure, serum uric acid, liver enzymes, and liver fat content while improving insulin sensitivity.

The Future

Innovent plans several additional clinical studies of mazdutide, including trials in adolescents with obesity, metabolic dysfunction-associated steatohepatitis, heart failure with preserved ejection fraction, and a higher-dose head-to-head study versus tirzepatide in moderate to severe obesity.

Specifically, the company has completed or is conducting 7 phase 3 clinical trials:

• GLORY-1, GLORY-2, and GLORY-3 for obesity and overweight
• GLORY-OSA for obstructive sleep apnea with obesity
• DREAMS-1, DREAMS-2, and DREAMS-3 for T2D

GLORY-1, DREAMS-1, DREAMS-2, and DREAMS-3 have already met their primary endpoints, the company said.