235-OR: Dorzagliatin as a Glucose Sensitizer Achieved Sustained Glycemic Control with Good Safety Profiles in Drug-Naïve T2D Patients in a 52-Week Phase 3 Monotherapy Trial (SEED)

Abstract

Improvement of glucose and insulin sensitivity in T2D remains as an unfulfilled task for the treatment of underlying cause of disease. Dorzagliatin is a first-in-class antidiabetic drug that acts as a glucose sensitizer, which repairs the sensor function of glucokinase(GK) and improves glucose sensitivity. The study aimed to confirm the efficacy and safety of dorzagliatin as a monotherapy in T2D patients. In this randomized, double-blind, placebo-controlled trial, 463 eligible drug-naïve Chinese patients were randomized to 75 mg dorzagliatin or placebo (2:1) twice daily (BID) groups for 24 weeks, followed by the dorzagliatin treatment (75 mg BID) for 28 weeks in both groups. The primary endpoint was the change in the HbA1c from baseline to week 24. The mixed models for repeated measures results suggested that the least squares mean change in HbA1c from baseline at week 24 was -1.07% in the dorzagliatin group, significantly lower than the placebo (P<0.0001), with effects sustained till the end of the 52-week treatment. Significantly improved β-cell function was seen at week 24 in the dorzagliatin group measured by the change in homeostasis model assessment 2-β (HOMA2-β) from baseline compared with the placebo group (2.56 vs. -0.72, P<0.05). The homeostatic control rate (HbA1c <7% without hypoglycemia) at week 24, was 42.2% in the dorzagliatin group compared to 17.3% in the placebo group (P<0.0001). No deaths, drug-related serious adverse events, and severe hypoglycemia were reported. Incidence of the clinically significant hypoglycemia (blood glucose <3.0 mmol/L) was low (<1%). Dorzagliatin had a favorable effect on sustained glycemic control and a good safety profile over 52 weeks in Chinese T2D patients. It is the first successful phase 3 trial for a GK activator. As a glucose sensitizer, dorzagliatin targets the restoration of glucose homeostasis, providing new hope for treating T2D patients. Disclosure L. Chen: None. Y. Zhang: Employee; Self; Hua Medicine. D. Zhu: None.