Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes.

Mazdutide is a once-weekly glucagon and glucagon-like peptide 1 receptor dual agonist developed for the treatment of type 2 diabetes (T2D). Here we report on a randomized phase III trial assessing the efficacy and safety of mazdutide, compared with dulaglutide, in participants with T2D who were also treated with background oral anti-diabetic drugs. In this study, 731 participants with T2D were randomized 1:1:1 to receive 4 mg mazdutide, 6 mg mazdutide or 1.5 mg dulaglutide for 28 weeks. Both doses of mazdutide showed non-inferiority and superiority to the 1.5-mg dose of dulaglutide in terms of the mean change in the diagnostic marker glycated haemoglobin A1c (HbA) from baseline to week 28, with a least-squares mean treatment difference of -0.24% (P = 0.0032) for 4 mg mazdutide and -0.30% (P = 0.0003) for 6 mg mazdutide, relative to 1.5 mg dulaglutide. Significantly greater reductions in body weight were achieved with mazdutide than with dulaglutide, with a least-squares mean treatment difference of -3.78% for 4 mg mazdutide and -5.76% for 6 mg mazdutide (both P < 0.0001), relative to dulaglutide. Moreover, significantly more participants who received mazdutide 4 mg or 6 mg reached the composite end point of HbA < 7.0% with a body-weight reduction of at least 5% at week 28 (both P < 0.0001), compared with those who received dulaglutide. The most common treatment-emergent adverse events were diarrhoea, nausea and vomiting. In summary, we found that in Chinese participants with T2D, 28 weeks of treatment with mazdutide (4 mg and 6 mg) provided reductions in HbA and body weight that were superior to those attained with 1.5 mg dulaglutide. Mazdutide was generally safe, although the incidence of gastrointestinal adverse events was higher for mazdutide than for dulaglutide.