Mazdutide Phase 2 Trial: A GLP-1/Glucagon Dual Agonist Cuts HbA1c and Body Weight in Diabetes
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- -7.1% body weight with mazdutide 6 mg over 20 weeks, compared to -2.7% with dulaglutide and -1.4% with placebo
- Evidence Grade:
- Strong evidence: well-designed randomized, double-blind, placebo-controlled trial published in Diabetes Care, though limited by phase 2 sample size and duration.
- Study Age:
- Published in 2024 in Diabetes Care. Represents active phase 2 clinical development of a novel dual-agonist peptide.
- Original Title:
- Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.
- Published In:
- Diabetes care, 47(1), 160-168 (2024)
- Authors:
- Zhang, Bo(2), Cheng, Zhifeng(5), 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
- Database ID:
- RPEP-09632
Evidence Hierarchy
Frequently Asked Questions
How is mazdutide different from tirzepatide?
Both are dual-agonist peptides, but they target different receptor pairs. Tirzepatide activates GLP-1 and GIP receptors, while mazdutide activates GLP-1 and glucagon receptors. Glucagon activation may offer unique benefits for fat burning and liver metabolism.
When will mazdutide be available?
Mazdutide is currently in clinical trials (phase 2 completed, phase 3 ongoing). If trials succeed and it receives regulatory approval, it could be available within a few years — but approval timelines are uncertain.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-09632APA
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
MLA
Zhang, Bo, et al. "Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.." Diabetes care, 2024. https://doi.org/10.2337/dc23-1287
RethinkPeptides
RethinkPeptides Research Database. "Efficacy and Safety of Mazdutide in Chinese Patients With Ty..." RPEP-09632. Retrieved from https://rethinkpeptides.com/research/zhang-2024-efficacy-and-safety-of-2
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.