A NEW phase 3 trial suggests that mazdutide, a once-weekly dual glucagon and glucagon-like peptide-1 (GLP-1) receptor agonist, may offer enhanced glycaemic control and weight reduction compared with dulaglutide in adults with type 2 diabetes. The findings add to growing interest in multi-agonist therapies that target both glucose regulation and energy balance.
Mazdutide has been developed to combine the established glucose-lowering effects of GLP-1 receptor agonism with glucagon-mediated effects on energy expenditure. In this randomised study, its efficacy and safety were evaluated against dulaglutide in people with type 2 diabetes receiving background oral anti-diabetic drugs.
Mazdutide Shows Superior HbA1c Reduction
The 28-week trial enrolled 731 participants, who were randomised to mazdutide 4 mg, mazdutide 6 mg, or dulaglutide 1.5 mg once weekly. Both doses of mazdutide met criteria for non-inferiority and demonstrated statistically significant superiority over dulaglutide in reducing HbA1c from baseline. Mean HbA1c reductions were greater with mazdutide 6 mg than with the 4 mg dose, suggesting a dose-response effect. For clinicians, the absolute differences in HbA1c, around 0.25–0.30 percentage points, may appear modest, but they were consistent and accompanied by additional metabolic benefits.
Greater Weight Loss and Composite Outcomes
Weight reduction was notably greater with mazdutide than with dulaglutide. Participants receiving mazdutide achieved mean additional weight losses of approximately 4–6% compared with dulaglutide, with the higher dose again producing larger effects. Importantly, more participants treated with mazdutide reached a clinically relevant composite endpoint of HbA1c below 7.0% alongside at least 5% weight loss. These combined outcomes reflect the dual-agonist mechanism and align with increasing emphasis on weight management as part of comprehensive type 2 diabetes care.
Safety Profile and Tolerability
Mazdutide was generally well tolerated over 28 weeks. Gastrointestinal adverse events, most commonly diarrhoea, nausea, and vomiting, were more frequent than with dulaglutide, consistent with other incretin-based therapies. Serious safety concerns were not highlighted in the study.
Putting the Findings in Context
Conducted in a Chinese population with type 2 diabetes, the trial shows that mazdutide can deliver greater improvements in glycaemic control and body weight than an established GLP-1 receptor agonist. While longer-term data and broader population studies will be needed, the results point to the potential role of dual-agonist therapies in future diabetes management without overstating their immediate clinical impact.
Reference
Guo L et al; DREAMS-2 investigators. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature. 2025; DOI:10.1038/s41586-025-10031-z.
