NatureType 2 DiabetesRCTDecember 17, 2025

Mazdutide versus placebo in Chinese adults with type 2 diabetes.

Zhu D, Zhao J, Cai H, Chu X, Xiu S, Song C, Cheng Z, Cao H, Jiang H, Zhang L, Wang H, Shi B, Li Y, Liu M, Feng B, Xue F, Deng H, Li H, Li L, Li Y, Ma Q, Qian L, DREAMS-1 Investigators

View on PubMed DOI: 10.1038/s41586-025-10026-w

Key Finding

Mazdutide, a dual-action diabetes drug, reduced blood sugar by 2.15% (HbA1c) and caused 7.81% weight loss in 24 weeks - both results that probably weren't just luck (p<0.0001).

What This Study Found

Think of mazdutide as a molecular multitasker - it's like having two specialized keys that unlock different doors in your body's metabolic system. One key targets the glucagon receptor (which normally raises blood sugar), while the other activates the GLP-1 receptor (which lowers blood sugar and reduces appetite). This dual approach is like having both the brake and accelerator for your blood sugar under better control. In this Chinese study of 320 people with type 2 diabetes, participants got weekly injections for 24 weeks. The results were striking: the higher dose (6mg) dropped HbA1c by 2.15 percentage points - imagine your blood sugar report card improving from a C+ to a B. Meanwhile, people lost an average of 7.81% of their body weight, which for a 180-pound person would be about 14 pounds. The side effects were typical GI issues you'd expect from this drug class - diarrhoea, nausea, and decreased appetite - essentially your digestive system adjusting to the new metabolic signals.

Statistics Decoded

HbA1c reduction of -2.15% vs -0.14% placebo means the drug lowered long-term blood sugar by about 2 full percentage points more than doing nothing - that's clinically massive. The p<0.0001 means there's less than a 1 in 10,000 chance this happened by pure luck. Weight loss of -7.81% vs -1.26% placebo means people lost nearly 8% of their body weight compared to barely 1% with placebo. More people hit the clinical jackpot: achieving both HbA1c under 7% (good diabetes control) AND losing 5%+ body weight - this composite endpoint shows the drug tackles both problems diabetes patients face.

Why This Matters

This represents a potential game-changer for diabetes care because it's the first drug to effectively target both blood sugar control AND weight loss with a single weekly injection, addressing the two biggest challenges diabetes patients face simultaneously.

Original Abstract

Despite advances in type 2 diabetes (T2D) management, unmet needs remain for therapies that effectively control hyperglycaemia while addressing the comorbid metabolic disorders1, 2. Here we assessed the efficacy and safety of the dual glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) agonist mazdutide monotherapy versus placebo in Chinese adults with T2D inadequately controlled with diet and exercise alone. In this phase 3 trial, 320 participants (mean HbA1c of 8.24%, BMI of 28.2 kg/m2, and diabetes duration of 1.9 years) were randomised 1:1:1 to receive weekly subcutaneous injections of mazdutide 4 mg, 6 mg, or placebo for 24 weeks, followed by a 24-week extended mazdutide treatment. At week 24, mazdutide significantly reduced HbA1c versus placebo (primary endpoint): -1.57% with mazdutide 4 mg and -2.15% with mazdutide 6 mg, versus -0.14% with placebo, with treatment differences of -1.43% and -2.02% (both p <0.0001). Significant weight loss at week 24 occurred with -5.61% (4 mg) and -7.81% (6 mg) versus -1.26% (placebo) (both p<0.0001). Additionally, significantly more participants with mazdutide achieved clinically relevant HbA1c target (<7.0%), weight loss goal (≥5%), and composite endpoints (HbA1c <7.0% and weight loss ≥5%) versus placebo (all p <0.0001). The most common adverse events-diarrhoea, decreased appetite, and nausea-were consistent with GLP-1R agonists. These results establish mazdutide monotherapy as an effective intervention providing clinically meaningful glycaemic control and weight reduction alongside a favourable safety profile in this population.