Innovent Biologics, a leading Chinese biopharmaceutical firm focused on oncology, metabolic, and autoimmune therapies, announced positive topline results from its fourth phase 3 trial, DREAMS-3 (NCT06184568), evaluating mazdutide (Xinermei®)—a once-weekly subcutaneous GLP-1 and glucagon (GCG) dual receptor agonist licensed exclusively from Eli Lilly for development in China. Originally discovered by Lilly, mazdutide targets both receptors to enhance glycemic control and promote significant weight loss, addressing the intertwined epidemics of T2D and obesity in China, where over 140 million adults live with T2D and obesity rates exceed 16%.
The multicenter, randomized, active-controlled DREAMS-3 study enrolled 349 adults aged 18–75 with inadequately controlled T2D (HbA1c 7.5–10.5%) and obesity (BMI ≥27.5 kg/m²). Participants, on stable metformin, were randomized 1:1 to receive mazdutide 6 mg or semaglutide 1 mg weekly for 32 weeks, followed by a 24-week extension for mazdutide patients based on weight loss targets. The dual primary endpoint assessed the proportion achieving HbA1c <7.0% and ≥10% weight loss from baseline at week 32, a rigorous composite reflecting real-world treatment goals.
Mazdutide demonstrated clear superiority: 48.0% of patients met the primary endpoint versus 21.0% on semaglutide (p<0.0001), marking the world’s first head-to-head phase 3 comparison of a GCG/GLP-1 dual agonist against semaglutide in T2D. Secondary analyses reinforced these benefits. Mean HbA1c reductions were -2.03% for mazdutide and -1.84% for semaglutide, with 78.6% versus 68.6% achieving HbA1c <7.0% alone. Weight loss was markedly greater at -10.29% (-8.2 kg) versus -6.00% (-4.7 kg), and more mazdutide patients hit ≥5% (89.4% vs. 70.3%) and ≥10% (60.9% vs. 28.6%) thresholds. Improvements extended to cardiometabolic markers, including systolic blood pressure and lipids, aligning with prior DREAMS-1 and DREAMS-2 trials that showed non-inferiority or superiority over placebo and dulaglutide.
Safety was comparable to class expectations, with treatment-emergent adverse events (TEAEs) primarily gastrointestinal (nausea, diarrhea, vomiting) in 62.6% of mazdutide versus 50.3% of semaglutide groups—mostly mild/moderate and transient during dose escalation. Serious TEAEs were low (2.3% vs. 1.7%), with no new signals; discontinuation rates were similar (7.4% vs. 6.9%). “DREAMS-3 underscores mazdutide’s potential as a transformative option for T2D patients with obesity, delivering dual benefits unmet by single-agonist therapies,” said Lei Qian, Innovent’s Chief R&D Officer for General Biomedicine. Principal investigator Prof. Linong Ji of Peking University People’s Hospital added, “With rising dual burdens of diabetes and obesity, mazdutide’s efficacy could meaningfully improve outcomes in China.”
Approved in China since June 2024 for chronic weight management (4 mg/6 mg), mazdutide’s T2D NDA is under review, with DREAMS-3 data supporting expanded labeling. Innovent plans full results at upcoming congresses, positioning mazdutide against global leaders like Ozempic® amid booming GLP-1 demand. This milestone enhances Innovent’s metabolic portfolio, potentially capturing significant market share in Asia’s underserved T2D population.
