115-LB: Dorzagliatin Showed Sustained Remission in an Observational Study after Discontinuation of Treatment in T2D Patients Who Achieved Good Glycemic Control with Dorzagliatin Monotherapy

Abstract

Diabetes remission is the optimal goal for treating T2D. While most remission studies focused on metabolic surgery, lifestyle interventions, and intensive insulin therapy, little evidence was found with oral antidiabetic drugs. Dorzagliatin is an oral dual-acting glucokinase activator which has shown effective glycemic control with significant improvements in early-phase insulin secretion and β-cell function. DREAM was an observational, non-pharmacological, non-interventional diabetes remission study, an extension study of a phase 3 monotherapy trial (SEED) with dorzagliatin. Initiated by investigators from 5 in 40 study sites in SEED, DREAM aimed to observe whether patients who had completed SEED and achieved good glycemic control were able to achieve diabetes remission without any antidiabetic medication. In total, 69 subjects previously with drug-naïve T2D and treated with dorzagliatin for 28 or 52 weeks in SEED were enrolled. The primary endpoint was the diabetes remission rate after 52 weeks of dorzagliatin withdrawal, estimated by the Kaplan-Meier method. At week 52, 36 subjects maintained stable glycemic control and the remission rate was 65.2% (95% CI, 53.4 to 77.0) . These 36 patients had shown improvement of early-phase insulin secretion (C30/G30) after dorzagliatin treatment in SEED. Improvements of β-cell function and insulin resistance were sustained during DREAM (indicated by HOMA2-β of 43.8 at baseline and 56.6 at week 52, HOMA2-IR of 1.58 at baseline and 1.46 at week 52) . According to a consensus released in Aug 2021 by ADA, diabetes remission was defined as HbA1c<6.5% measured at least 3 months after cessation of glucose-lowering pharmacotherapy. Based on this definition, the remission rate was 52.0% (95% CI, 31.2 to 69.2) . DREAM observed sustained glycemic control in a high proportion of subjects after withdrawal of dorzagliatin monotherapy, indicating that improvements of early-phase insulin secretion and β-cell function may be a potential mechanism for diabetes remission. Disclosure J. Zeng: None. S. Gan: None. X. Dong: None. Y. Liu: None. X. Su: None. J. Luo: None. J. Ma: None.