The SEED study of dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, phase 3 trial

Abstract Improvement of glucose and insulin sensitivity remains an unmet medical need in diabetes management, in which the underlying cause of type 2 diabetes(T2D) was not well addressed by current treatment. We report the findings of a randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03173391) to evaluate the efficacy and safety of dorzagliatin, a dual-acting glucokinase (GK) allosteric modulator, which enhances the GK activity in T2D patients in a glucose dependent manner, and has demonstrated its effects in blood glucose control through improvement of glucose sensitivity in T2D patients. Eligible drug-naïve T2D patients (n=463) were randomly assigned to dorzagliatin group or placebo group in a 2:1 ratio for a 24-week double-blind treatment, then followed by a 28-week open-label treatment with dorzagliatin in all patients. The primary efficacy endpoint was the change from baseline in the glycated hemoglobin (HbA1c) level at week 24. Safety was assessed throughout the trial. At week 24, the change from baseline in HbA1c was -1.07% in the dorzagliatin group and -0.50% with placebo (ETD, -0.57%; 95%CI, -0.79 to -0.36; P<0.001), and the effects sustained through 52 weeks. Improvement of β-cell function was demonstrated by an increase of HOMA2-β in dorzagliatin group over placebo group (2.56 vs -0.72; 95% CI, 0.44 to 6.11; P<0.05) at week 24. The incidence of adverse events(AEs) was similar between the two groups during the 24 weeks and most AEs were mild during 52 weeks. There were no severe hypoglycemia events and drug related serious adverse events. The incidence of hypoglycemia was 1 of 310 patients (0.3%) in the dorzagliatin group during the 24 weeks. There was no body weight gain during the study period. In drug-naïve T2D patients, dorzagliatin demonstrated fast onset and sustained glycemic control with a good safety and tolerability profile for 52 weeks.