Mazdutide, a once-weekly GLP-1/glucagon dual agonist, reduced HbA1c by up to 1.67% and body weight by up to 7.1% over 20 weeks in a phase 2 trial of 250 patients with type 2 diabetes.
-7.1% body weightwith mazdutide 6 mg over 20 weeks, compared to -2.7% with dulaglutide and -1.4% with placebo
What the researchers found
Mazdutide 6 mg reduced HbA1c by 1.67% and body weight by 7.1% over 20 weeks, significantly exceeding both placebo and the reference GLP-1 drug dulaglutide on weight loss endpoints.
Why it matters
While tirzepatide targets GLP-1/GIP, mazdutide targets GLP-1/glucagon — a different dual-agonist approach. Glucagon co-activation may enhance fat burning and liver fat reduction beyond what GLP-1 alone achieves, potentially offering unique metabolic benefits.
The numbers in context
203 patients randomized: 51 to 3 mg, 49 to 4.5 mg, 53 to 6 mg mazdutide, and 50 to placebo. HbA1c range at entry: 7.0-10.5%.
How the study worked
Randomized, double-blind, placebo-controlled phase 2 trial. 250 Chinese adults with T2D (HbA1c 7.0-10.5%) randomized to mazdutide 3 mg (n=51), 4.5 mg (n=49), 6 mg (n=49), open-label dulaglutide 1.5 mg (n=50), or placebo (n=51) for 20 weeks. Primary endpoint: HbA1c change at week 20.
Who was studied
203 Chinese adults with type 2 diabetes (HbA1c 7.0-10.5%) on metformin or diet/exercise
What this study cannot tell us
Phase 2 trial with moderate sample size and 20-week duration. Studied only in Chinese patients — efficacy in other populations needs confirmation. Open-label dulaglutide arm introduces potential bias. GI side effects were common (36% diarrhea). Long-term safety of glucagon co-activation unknown.
How to read the evidence
Strong evidence: well-designed randomized, double-blind, placebo-controlled trial published in Diabetes Care, though limited by phase 2 sample size and duration.
When this study was published
Published in 2024 in Diabetes Care. Represents active phase 2 clinical development of a novel dual-agonist peptide.
The bigger picture
The GLP-1 drug landscape is expanding rapidly beyond single-target agonists. Mazdutide represents the GLP-1/glucagon pathway (alongside survodutide), while tirzepatide represents GLP-1/GIP. Both dual-agonist strategies aim to surpass single GLP-1 drugs, but through different mechanisms. The coming years will reveal which approach — or combination — delivers the best metabolic outcomes.
Questions still open
- How does mazdutide compare head-to-head with tirzepatide (GLP-1/GIP agonist)?
- Does glucagon co-activation provide specific benefits like liver fat reduction beyond what GLP-1/GIP dual agonists achieve?
- Will mazdutide phase 3 trials confirm these results in larger, more diverse populations?
Common questions
How is mazdutide different from tirzepatide?
When will mazdutide be available?
Read the original research
Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.
Diabetes care, 47(1), 160-168
Citation
Zhang, Bo; Cheng, Zhifeng; Chen, Ji; Zhang, Xin; Liu, Dexue; Jiang, Hongwei; Ma, Guoqing; Wang, Xiaoyun; Gan, Shenglian; Sun, Juan; Jin, Ping; Yi, Jianjun; Shi, Bimin; Ma, Jianhua; Ye, Shandong; Wang, Guixia; Ji, Linong; Gu, Xuejiang; Yu, Ting; An, Pei; Deng, Huan; Li, Haoyu; Li, Li; Ma, Qingyang; Qian, Lei; Yang, Wenying. (2024). Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.. Diabetes care, 47(1), 160-168. https://doi.org/10.2337/dc23-1287