Mazdutide versus placebo in Chinese adults with type 2 diabetes
Article Date: 17 December 2025
Article URL: https://www.nature.com/articles/s41586-025-10026-w
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Summary
This Phase 3 randomised trial (DREAMS-1) assessed mazdutide, a dual glucagon receptor (GCGR)/GLP-1 receptor (GLP-1R) agonist, as monotherapy versus placebo in 320 Chinese adults with type 2 diabetes inadequately controlled with diet and exercise. Participants had a mean baseline HbA1c of 8.24%, BMI 28.2 kg/m2 and diabetes duration about 1.9 years. Over 24 weeks, weekly subcutaneous mazdutide at 4 mg and 6 mg produced large, statistically significant improvements in glycaemic control and body weight compared with placebo. The safety profile was consistent with known GLP-1R agonist effects.
Key Points
- Design: Phase 3, randomised 1:1:1, 320 participants, 24-week double-blind period with a 24-week extension.
- Baseline: mean HbA1c 8.24%, mean BMI 28.2 kg/m2, mean diabetes duration 1.9 years.
- Primary outcome (week 24): HbA1c reductions of -1.57% (mazdutide 4 mg) and -2.15% (6 mg) versus -0.14% with placebo; treatment differences -1.43% and -2.02% (both p<0.0001).
- Weight loss (week 24): mean -5.61% (4 mg) and -7.81% (6 mg) versus -1.26% for placebo (both p<0.0001).
- More participants on mazdutide achieved clinically relevant targets: HbA1c <7.0%, weight loss ≥5%, and the composite of both (all comparisons p<0.0001 vs placebo).
- Common adverse events: diarrhoea, decreased appetite and nausea — consistent with GLP-1R agonists; overall safety described as favourable in this population.
- Conclusion: Mazdutide monotherapy delivered clinically meaningful glycaemic control and weight reduction in this Chinese T2D cohort.
Content summary
The DREAMS-1 trial shows that weekly mazdutide significantly lowers HbA1c and reduces body weight over 24 weeks compared with placebo in adults with type 2 diabetes not controlled by lifestyle alone. The 6 mg dose produced greater reductions than 4 mg (approximately -2.15% v -1.57% HbA1c). Weight reductions were substantial, approaching levels often targeted for cardio-metabolic benefit. Safety signals aligned with expectations for GLP-1 receptor agonism; no unexpected safety concerns were reported in the main text of the preview manuscript.
Context and relevance
Mazdutide is part of an expanding class of incretin-based and dual-agonist therapies being investigated to treat both hyperglycaemia and excess weight. The magnitude of HbA1c and weight reductions here is notable and relevant to clinicians, diabetes researchers and industry: a single agent producing meaningful improvements in both glucose control and body weight could simplify treatment pathways. The study is limited to Chinese adults and to a 24-week primary endpoint — longer-term outcomes, cardiovascular safety data and broader population studies will be needed to define its place in routine care.
Author note (style: punchy)
Quick read: mazdutide packs a punch. Big falls in HbA1c and body weight in 24 weeks — the 6 mg dose especially impressive. If you care about new diabetes meds or the shifting treatment landscape where weight and glucose are tackled together, this is worth a proper look.
Why should I read this?
Short and honest: if you want to know whether a new dual GCGR/GLP-1R drug can meaningfully cut blood sugar and body weight as a single therapy, this paper gives a clear early answer. Saves you digging through full trial data — highlights the effect sizes, side-effect profile and why clinicians and drug developers are excited.