763-P: Dorzagliatin Add-On to Metformin Achieved Sustained Efficacy and Good Safety Profiles in T2D Patients in a 52-Week Phase 3 Trial (DAWN)

Abstract

Metformin, as recommended in various guidelines, is the currently preferred first-line treatment for T2D and often used in combination with other antidiabetic agents. Despite advances in diabetes therapeutics, there was still a lack of improvement in reaching clinical targets. Previous results on dorzagliatin from a monotherapy trial (SEED) have shown sustained efficacy and safety profiles in drug-naive T2D patients over 52 weeks. In this randomized, double-blind, placebo-controlled trial, the efficacy and safety of dorzagliatin add-on to metformin in T2D patients were evaluated. Patients were treated with metformin at 1500 mg/day as basic therapy throughout the 52-week treatment period. A total of 767 eligible Chinese patients were randomized to 75 mg dorzagliatin or placebo (1:1) BID groups for 24 weeks, followed by another 28 weeks with dorzagliatin (75 mg BID) in both groups. The primary endpoint was the change of the HbA1c from baseline at week 24. The HbA1c from baseline was reduced by 1.02% at week 24 in the dorzagliatin group, superior to the placebo (P<0.0001), with effects sustained till the end of the 52-week treatment. The target response rate (HbA1c <7.0%) at week 24, was 44.4% in the dorzagliatin group compared to 10.7% in the placebo group (P<0.0001). At week 24, the 2h-PPG was reduced from baseline by 5.45 mmol/L with dorzagliatin, significantly lower than placebo (P<0.0001). Dorzagliatin significantly improved β-cell function at week 24, as measured by HOMA2-β and HOMA2-IR (P<0.05). No drug-related serious adverse events, and severe hypoglycemia were reported. There was less than 1% hypoglycemia (blood glucose <3.0 mmol/L) during the 52 weeks. With a novel mechanism of action, dorzagliatin add-on to metformin has shown sustained glycemic control and good safety profiles over 52 weeks, offering a new solution to T2D patients with insufficiently controlled blood glucose on metformin. Disclosure L. Chen: None. Y. Zhang: Employee; Self; Hua Medicine. W. Yang: None.