Mazdutide Beats Dulaglutide in Phase 3 Diabetes Trial

Innovent Biologics, Inc., a leading biopharmaceutical company known for developing treatments for several significant diseases, has announced the success of its Phase 3 clinical trial, DREAMS-2, for mazdutide (IBI362). This dual agonist targeting glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) demonstrated superior efficacy in Chinese patients with type 2 diabetes (T2D) compared to dulaglutide, particularly in glycemic control and multiple cardiometabolic benefits.

The DREAMS-2 study is a comprehensive, multi-center, randomized clinical trial that engaged 731 Chinese subjects with T2D, who had insufficient glycemic control despite using metformin as monotherapy or in combination with other oral drugs. Participants were assigned to receive either 4.0 mg or 6.0 mg of mazdutide or 1.5 mg of dulaglutide over 28 weeks. The primary analysis centered on the change in glycated hemoglobin (HbA1c) levels from the baseline to week 28. Upon attaining non-inferiority, further tests confirmed mazdutide’s superiority over dulaglutide.

Both dosages of mazdutide (4.0 mg and 6.0 mg) showed significant HbA1c reduction compared to dulaglutide, reaching the primary endpoint of the study. Secondary endpoints also highlighted mazdutide’s broader benefits, such as enhanced weight loss, reduced blood pressure, and improved lipid profiles. Besides lowering glucose levels and body weight, mazdutide exhibited substantial advantages in a range of cardiometabolic metrics, including serum uric acid, liver enzymes, and blood pressure.

The safety and tolerability profile of mazdutide was favorable. The most common side effects were gastrointestinal but were generally mild to moderate and transient. No severe hypoglycemia was reported, and the incidence of hypoglycemia was minimal, aligning with or better than dulaglutide and other established GLP-1 drugs. Cardiovascular risk signals were similar to dulaglutide, ensuring a robust safety profile.

Innovent's mazdutide is the first dual GLP-1R/GCGR agonist progressing through regulatory review for chronic weight management. The results from DREAMS-2 provide critical evidence supporting mazdutide’s effectiveness for T2D patients in China. The company anticipates releasing data from another ongoing Phase 3 study, DREAMS-1, and aims to submit an FDA application for T2D management in mid-2024.

The clinical researchers, including Professors Lixin Guo and Yang Wenying, underscored the significance of DREAMS-2, highlighting its clinical and academic value. They noted mazdutide’s comprehensive benefits beyond glycemic reduction, addressing urgent needs in managing T2D with comorbidities such as obesity and hypertension, common among Chinese patients.

Dr. Lei Qian, Vice President of Clinical Development at Innovent, emphasized the necessity for innovative diabetes treatments in China. He affirmed that mazdutide’s superior efficacy over dulaglutide promises a new, potent therapeutic option for Chinese patients with T2D. The company plans further analyses and a swift regulatory submission to enhance treatment access.

Mazdutide’s development stems from a partnership between Innovent and Eli Lilly and Company (Lilly), designed to bring this GLP-1R and GCGR dual agonist to the Chinese market. Clinical trials have demonstrated significant weight loss and glucose-lowering effects, alongside broader cardiometabolic benefits, supporting its potential as a transformative therapy for T2D and other metabolic conditions.