NatureType 2 DiabetesRCTDecember 17, 2025

Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes.

Guo L, Zhang B, Xue X, Zhang X, Cai H, Jiang H, Zhang L, Jin P, Wang X, Cheng Z, Zhang S, Geng J, Guo Y, Hu H, Ma Q, Li L, Du H, Han-Zhang H, Xue F, Deng H, Qian L, Yang W, DREAMS-2 investigators

View on PubMed DOI: 10.1038/s41586-025-10031-z

Key Finding

Mazdutide, a dual-hormone diabetes drug, beat dulaglutide by lowering blood sugar an extra 0.24-0.30% and causing 3.78-5.76% more weight loss over 28 weeks in Chinese adults with type 2 diabetes.

What This Study Found

Think of mazdutide as a diabetes drug with a dual personality - it activates both glucagon and GLP-1 receptors, like having two different keys that unlock complementary pathways for blood sugar control and weight loss. In this head-to-head competition involving 731 Chinese adults with type 2 diabetes, researchers pitted two doses of mazdutide (4mg and 6mg weekly injections) against the established champion dulaglutide (1.5mg weekly). After 28 weeks, mazdutide didn't just match dulaglutide - it clearly outperformed it. The blood sugar improvements (measured by HbA1c) were like upgrading from a good result to an excellent one, with mazdutide providing an additional 0.24-0.30% reduction beyond what dulaglutide achieved. But the real showstopper was weight loss: if dulaglutide helped people lose weight, mazdutide helped them lose significantly more - imagine the difference between losing 10 pounds versus losing 13-16 pounds. However, this extra effectiveness came with a trade-off: more people experienced the classic GLP-1 side effects of nausea, vomiting, and diarrhea - like a more powerful engine that runs a bit rougher.

Statistics Decoded

The p-values of 0.0032 and 0.0003 for blood sugar improvements mean this wasn't just lucky - like flipping heads 300+ times in a row, we can be very confident mazdutide truly works better. The HbA1c differences of -0.24% and -0.30% might seem small, but in diabetes management, every 0.1% reduction matters significantly for long-term complications. The weight loss differences of -3.78% and -5.76% mean if someone weighs 200 pounds, they'd lose about 7-11 more pounds with mazdutide compared to dulaglutide. The 'both p<0.0001' for the composite endpoint means the chance this happened by coincidence is less than 1 in 10,000 - essentially impossible.

Why This Matters

This gives doctors and patients a potentially superior option for managing type 2 diabetes, especially for those who need both better blood sugar control and meaningful weight loss in a single weekly injection. For the competitive diabetes drug market, it suggests dual-hormone approaches may represent the next evolution beyond current GLP-1 therapies.

Original Abstract

Mazdutide is a once-weekly glucagon and glucagon-like peptide-1 receptor dual agonist developed for the treatment of type 2 diabetes (T2D) 1. This study assessed the efficacy and safety of mazdutide versus dulaglutide in participants with T2D on background oral anti-diabetic drugs. In this randomised phase 3 study, 731 participants with T2D were randomised 1:1:1 to receive mazdutide 4 mg, mazdutide 6 mg or dulaglutide 1.5 mg for 28 weeks. Both mazdutide doses demonstrated non-inferiority and superiority to dulaglutide 1.5 mg in mean change in HbA1c from baseline to week 28, with the least squares (LS) mean treatment difference of -0.24% (p=0.0032) for mazdutide 4 mg and -0.30% (p=0.0003) for mazdutide 6 mg vs dulaglutide 1.5 mg. Significantly greater weight reductions were achieved with mazdutide versus dulaglutide, with LS mean treatment difference of -3.78% for mazdutide 4 mg and -5.76% for mazdutide 6 mg vs dulaglutide (both p<0.0001). Moreover, significantly more participants with mazdutide achieved the composite endpoint of HbA1c <7.0% with ≥5% weight reduction vs dulaglutide 1.5 mg at week 28 (both p<0.0001). The most common treatment-emergent adverse events were diarrhoea, nausea, and vomiting. Our findings showed that 28-week treatment with mazdutide (4 mg and 6 mg) provided superior reductions in HbA1c and body weight compared with dulaglutide 1.5 mg in Chinese participants with T2D. Mazdutide was generally safe, with a higher incidence of gastrointestinal adverse events than dulaglutide.