Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 2 trial
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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.
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With mazdutide treatment, 51% of participants experienced nausea and 43% experienced vomiting, but drug discontinuation due to adverse events was low at 2%.
“With mazdutide treatment, 51% of participants experienced nausea and 43% experienced vomiting, but drug discontinuation rate due to adverse events was low (2%; table).126,134”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [126]
Table 2 in the Results reports nausea in 21.6–24.5% and vomiting in 11.8–16.3% of mazdutide recipients across the three dose groups, not 51% and 43%. It reports no adverse events leading to treatment discontinuation in the mazdutide groups; the 2% figure belongs to the dulaglutide group. (LLM, conf=0.94)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn a phase 2 clinical trial among Chinese patients, mazdutide reduced HbA1c by −1.41% to −1.67% in a dose dependent manner compared to +0.03% for placebo.
“In a phase 2 clinical trial among Chinese patients, mazdutide reduced HbA1c by −1.41% to −1.67% in a dose dependent manner compared to +0.03% for placebo.31”
From GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review (2024) · cites this paper as [31]
The Results report the stated week-20 HbA1c changes for mazdutide (−1.41% to −1.67%) and placebo (0.03%). But the Conclusions say the greatest reduction occurred at 4.5 mg, not the highest 6 mg dose, and that clear dose dependence in HbA1c reduction may not be evident. Page numbers were not supplied. (LLM, conf=0.91)
Experimental — accuracy not yet measuredBodyweight was reduced more by all doses of mazdutide (3-6 mg/week) than by dulaglutide.
“Bodyweight was reduced more by all doses of mazdutide (ie, 3-6 mg/week) than by dulaglutide.126”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [126]
In a phase 2 trial in people with type 2 diabetes, after 20 weeks, mazdutide up to 6 mg weekly reduced HbA1c numerically more (up to 1.7% [19 mmol/mol]) than dulaglutide (1.4% [15 mmol/mol]).
“In a phase 2 trial in people with type 2 diabetes, after 20 weeks of treatment, mazdutide (up to 6 mg weekly) reduced HbA 1c numerically more (by up to 1•7% [19 mmol/mol]) compared with the selective GLP-1 receptor agonist dulaglutide (HbA 1c reduction of 1•4% [15 mmol/mol]).126”
From GLP-1 receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits (2026) · cites this paper as [126]
The magnitude of weight loss with retatrutide exceeded that seen with other pipeline multi-agonists such as CagriSema, mazdutide and survodutide.
“Moreover, the magnitude of WL with retatrutide also exceeded that seen with other pipeline multi-agonists such as CagriSema (cagrilintide, an amylin agonist, in combination with semaglutide), mazdutide and survodutide (Fig. 4) [8, 27, 35, 36, 45, 46, 49–53].”
From Triple Agonism Based Therapies for Obesity (2025) · cites this paper as [52]
In people with T2D, mazdutide (3, 4.5, 6 mg) in a phase 2 trial reduced HbA1c up to −1.7% and body weight up to 7.1% at 20 weeks.
“For people with T2D, a phase 2 trial with mazdutide (doses 3, 4.5 and 6 mg) has shown reduction in HbA1c (up to −1.7%) and up to 7.1% WL at 20 weeks (Table 3), while early phase trials for MASH are in progress [72].”
From What is the pipeline for future medications for obesity? (2025) · cites this paper as [72]
The SAEs with mazdutide were similar to dulaglutide and placebo groups with no participant discontinuing mazdutide due to AEs.
“The SAEs with mazdutide were similar to the dulaglutide and placebo groups with no participant discontinuing mazdutide due to AEs.”
In a phase 2 trial of 20 weeks, mazdutide (3, 4.5 and 6 mg) in a Chinese population with T2D resulted in mean HbA1c change ranging from −1.41% to −1.67% compared to −1.35% with dulaglutide and +0.03% with placebo.
“A phase 2 trial of 20 weeks duration assessed the safety and efficacy of three different doses of mazdutide (3, 4.5 and 6 mg) in a Chinese population with T2D [72]. The mean HbA1c change ranged from −1.41% to −1.67% with mazdutide (maximum efficacy with mazdutide 4.5 mg) compared to −1.35% with dulaglutide and + 0.03% with placebo.”
Mazdutide improved cardiometabolic risk factors such as waist circumference, blood pressure and lipids.
“Mazdutide improved also cardiometabolic risk factors such as waist circumference, blood pressure and lipids.”
Mazdutide 6 mg achieved mean WL 7.1%, compared to 2.7% WL with dulaglutide and 1.4% WL with placebo.
“There was also a dose-dependent effect on body weight, with mazdutide 6 mg achieving mean WL 7.1%, compared to 2.7% WL with dulaglutide and 1.4% WL with placebo.”
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- Authors
- Zhang, B., Cheng, Z., Chen, J., Zhang, X., Liu, D., Jiang, H., Ma, G., Wang, X., Gan, S., Sun, J., Jin, P., Yi, J., Shi, B., Ma, J., Ye, S., Wang, G., Ji, L., Gu, X., Yu, T., An, P., Deng, H., Li, H., Li, L., Ma, Q., Qian, L., & Yang, W.
- Affiliations
- China-Japan Friendship Hospital (CN)
- Harbin Medical University (CN)
- Innovent Biologics (China) (CN)
- 4Department of Endocrinology and Metabolism, Genertec Liaoyou Gem Flower Hospital, Panjin, China
- Nanyang Medical College (CN)
- Henan University of Science and Technology (CN)
- Heilongjiang University of Chinese Medicine (CN)
- Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province (CN)
- The First People's Hospital of Changde (CN)
- Affiliated Hospital of Xuzhou Medical College (CN)
- Third Xiangya Hospital (CN)
- 12Department of Endocrinology, First People’s Hospital of Xiangtan City, Xiangtan, China
- First Affiliated Hospital of Soochow University (CN)
- Nanjing First Hospital (CN)
- Anhui Provincial Hospital (CN)
- First Hospital of Jilin University (CN)
- Peking University People's Hospital (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Corresponding author
- Yang, Wenying
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2023-11-09
- Volume
- 47
- Issue
- 1
- Pages
- 160-168
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC10733643
- OpenAlex
- W4388539816
- Cited by
- 91
- References
- 21
- Citations by year
- 2026: 37 · 2025: 35 · 2024: 19
- FWCI
- 18.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Innovent Biologics
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- mazdutide, type 2 diabetes, GLP-1 receptor agonists, glucagon receptor agonist, dual agonist, HbA1c, weight loss, dulaglutide, adverse events, hypoglycemia, Chinese patients
- MeSH terms
- Adult, Body Weight, China, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Glucagon-Like Peptides, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Peptides, Treatment Outcome, Glucagon-Like Peptide 1
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