Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial.

BACKGROUND: Effective weight management and glycemic control are both important in people with type 2 diabetes (T2D) and obesity. Despite the proven benefits of GLP-1 receptor agonists, there is a persistent need for more effective weight management strategies in the treatment of T2D and obesity. Glucagon receptor-based co-agonists, such as mazdutide, represent a promising therapeutic class with the potential for enhanced weight loss compared to current standards of care. However, robust clinical evidence for these agents in populations with T2D and obesity is still lacking. The DREAMS-3 trial is designed to address this gap by directly comparing the efficacy and safety of mazdutide against semaglutide, a widely used GLP-1 receptor agonist, in Chinese adults with T2D and obesity. The results will provide crucial evidence to inform clinical decision-making for this large patient population. METHODS: DREAMS-3 is a randomized, open-label phase 3 trial. Obese Participants (BMI ≥ 28 kg/m) diagnosed with T2D (≤ 10 years) who had inadequate glycemic control after diet and exercise alone with/without metformin were randomized in a 1:1 ratio to receive mazdutide 6 mg or semaglutide 1 mg once weekly in the 32-week active-controlled treatment period, followed with a 24-week extension period. The primary endpoint is the proportion of participants achieving glycated hemoglobin <7.0 % and weight reduction of ≥10 % at week 32. RESULTS: A total of 349 participants were enrolled and randomized, the overall mean age was 42.4 years, 44.7 % of participants were male. The mean baseline duration of T2D was 1.8 years, and 39.5 % of participants were on metformin. The mean glycated hemoglobin was 8.0 %, body weight was 90.5 kg, BMI was 33.0 kg/m. Most participants had at least one comorbidity. The prevalence of some comorbidities (such as metabolic associated fatty liver disease, gout/hyperuricemia) showed strong association of BMI. CONCLUSION: DERAMS-3 is the first head-to-head trial to compare the efficacy and safety of mazdutide versus semaglutide in Chinese adults with T2D and obesity, with an expected completion date in early 2026.