Innovent Biologics announced positive results from multiple clinical studies of mazdutide, a GLP-1R/GCGR dual agonist, at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting. The data highlight mazdutide's efficacy in managing type 2 diabetes and obesity, with significant improvements in glycemic control, weight loss, and cardiometabolic risk factors.
DREAMS-2: Mazdutide vs. Dulaglutide in Type 2 Diabetes
The Phase 3 DREAMS-2 trial (NCT05606913) compared mazdutide to dulaglutide in 731 Chinese adults with type 2 diabetes inadequately controlled by metformin and/or other oral anti-diabetic medications. After 28 weeks, mazdutide (4mg and 6mg) demonstrated superior reductions in HbA1c compared to dulaglutide 1.5mg (1.69% and 1.73% vs 1.36%, respectively). Furthermore, a greater proportion of patients on mazdutide achieved HbA1c <7.0% (71.2% and 74.2% vs 62.1% with dulaglutide).
Mazdutide also outperformed dulaglutide in weight reduction. Participants treated with mazdutide 4 mg and 6 mg experienced mean weight reductions of 9.24% and 7.13%, respectively, compared to 2.86% with dulaglutide. A significantly higher percentage of mazdutide-treated participants achieved a weight reduction of ≥5% (62.4% and 78.2% vs 26.9% for dulaglutide).
Professor Lixin Guo, the principal investigator, noted that mazdutide represents a new generation of GLP-1 therapies for type 2 diabetes, offering improved glucose control, weight management, and a favorable safety profile.
GLORY-1: Mazdutide in Overweight and Obese Individuals
The Phase 3 GLORY-1 trial evaluated mazdutide in 610 Chinese patients who were either overweight or obese. Patients achieved 10.97% and 13.38% reduction in body weight compared to baseline with 4mg and 6mg mazdutide, respectively. At 48 weeks, more than half of patients (50.6%) on high-dose mazdutide reported at least a 15% reduction in body weight.
Exploratory data also revealed a dose-dependent reduction in liver fat content (LFC). Mean LFC reductions of 7.7% and 13.6% were observed with 4 mg and 6 mg mazdutide, respectively, compared to a 0.8% reduction with placebo.
Additional Metabolic Benefits
In both trials, mazdutide demonstrated improvements in various cardiometabolic risk factors, including systolic blood pressure, triglyceride, cholesterol, LDL levels, serum uric acid, and alanine aminotransferase levels. These benefits were generally more pronounced with mazdutide compared to dulaglutide or placebo.
Regulatory Status and Future Directions
Mazdutide, initially developed by Eli Lilly, is under regulatory review in China for both chronic weight management and glycemic control in type 2 diabetes. Innovent has two NDAs accepted by China's NMPA for review.
Dr. Lei Qian, Vice President of Clinical Development of Innovent, expressed optimism about mazdutide's potential to benefit a large number of patients seeking improvements in glycemic control, weight management, and cardiovascular metabolic indicators.
Currently, Innovent is conducting five Phase 3 trials evaluating mazdutide in Chinese patients with type 2 diabetes, obesity, or both. The DREAMS-1, GLORY-1 and DREAMS-2 studies have already reached their primary endpoints.
