Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

Abstract

Objective: We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of mazdutide, a once-weekly glucagon-like peptide 1 and glucagon receptor dual agonist, in Chinese patients with type 2 diabetes.

Research design and methods: Adults with type 2 diabetes inadequately controlled with diet and exercise alone or with stable metformin (glycated hemoglobin A1c [HbA1c] 7.0-10.5% [53-91 mmol/mol]) were randomly assigned to receive 3 mg mazdutide (n = 51), 4.5 mg mazdutide (n = 49), 6 mg mazdutide (n = 49), 1.5 mg open-label dulaglutide (n = 50), or placebo (n = 51) subcutaneously for 20 weeks. The primary outcome was change in HbA1c from baseline to week 20.

Results: Mean changes in HbA1c from baseline to week 20 ranged from -1.41% to -1.67% with mazdutide (-1.35% with dulaglutide and 0.03% with placebo; all P < 0.0001 vs. placebo). Mean percent changes in body weight from baseline to week 20 were dose dependent and up to -7.1% with mazdutide (-2.7% with dulaglutide and -1.4% with placebo). At week 20, participants receiving mazdutide were more likely to achieve HbA1c targets of <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) and body weight loss from baseline of ≥5% and ≥10% compared with placebo-treated participants. The most common adverse events with mazdutide included diarrhea (36%), decreased appetite (29%), nausea (23%), vomiting (14%), and hypoglycemia (10% [8% with placebo]).

Conclusions: In Chinese patients with type 2 diabetes, mazdutide dosed up to 6 mg was generally safe and demonstrated clinically meaningful HbA1c and body weight reductions.

Graphical abstract

Figure 1

Participant flow.

Figure 2

Changes in HbA_1c, fasting plasma glucose (FPG), and body weight over time; proportion of participants achieving HbA_1c and weight loss targets; and self-measured blood glucose (SMBG) profiles. A: Change from baseline in HbA_1c over time. B: Proportion of participants reaching HbA_1c targets. C: Change from baseline in FPG over time. D: SMBG profiles at baseline and week 20. E: Percent change from baseline in body weight over time. F: Proportion of participants reaching weight loss targets. Data in A, C, D, and E are plotted as least squares mean ± SE from an MMRM analysis of the mITT population. Proportion of participants reaching HbA_1c (B) or weight loss (F) targets was obtained by dividing the number of participants reaching the respective target at week 20 by the number of participants in the mITT population. Participants numbers were as follows: 3 mg mazdutide n = 50, 4.5 mg mazdutide n = 48, 6 mg mazdutide n = 49, placebo n = 51, and dulaglutide n = 50.