306-OR: Mazdutide vs. Placebo as Monotherapy in Patients with Type 2 Diabetes (DREAMS-1)

Introduction and Objective: Mazdutide (MAZ) is a once-weekly GLP-1 and glucagon receptor dual agonist in development for type 2 diabetes (T2D). This trial assessed the efficacy and safety of MAZ vs placebo (PBO) in patients with T2D inadequately controlled by diet and exercise alone. Methods: In this randomized, 24-week double-blind, placebo-controlled phase 3 trial, 320 patients with T2D (mean baseline HbA1c 8.24%, age 50.4 yrs, diabetes duration 1.9 yrs, body weight 77.7 kg) were randomised 1:1:1 to receive MAZ 4 mg, 6 mg or PBO. Primary endpoint was mean change in HbA1c from baseline at week 24. Secondary endpoints included proportion of patients achieving HbA1c and weight reduction targets and mean percentage change in weight from baseline at week 24. Results: At week 24, MAZ was superior to PBO in mean HbA1c change from baseline (LSM treatment difference: −1.43% [95% CI −1.73, −1.13] for MAZ 4 mg; −2.02% [−2.32, −1.72] for MAZ 6 mg; both p<0.0001). MAZ was superior to PBO in proportion of patients achieving HbA1c <7.0%, weight reduction ≥5%, both HbA1c <7.0% and body weight reduction ≥5%, as well as mean percentage change in weight from baseline at week 24 (Table). The most common adverse events were gastrointestinal and mostly mild to moderate in severity. No severe hypoglycemia was reported. Conclusion: In Chinese patients with T2D, MAZ as monotherapy demonstrated robust and clinical meaningful HbA1c and body weight reduction. Disclosure D. Zhu: Consultant; Innovent Biologics. J. Zhao: None. H. Cai: None. X. Chu: Consultant; Innovent Biologics. S. Xiu: Consultant; Innovent Biologics. C. Song: Consultant; Innovent Biologics. Z. Cheng: None. H. Cao: None. H. Jiang: None. L. Zhang: None. F. Xue: None. H. Deng: Employee; Innovent Biologics. H. Li: None. L. Li: Employee; Innovent Biologics. Stock/Shareholder; Innovent Biologics. L. Qian: Employee; Innovent Biologics. Funding Innovent Biologics, Inc.