117-LB: Glucokinase Activator Restores Glucose Sensitivity and Early-Phase Insulin Secretion in T2DM Patient—A Post Hoc Analysis of Dorzagliatin

Abstract

Background: Insulinogenic index (IGI) and disposition index (DI) measures patient’s early phase insulin secretion ability and glucose sensitivity. Pervious clinical trials of dorzagliatin have showed excellent effect on glycemic control and good safety profile in Chinese T2DM patients. This post-hoc analysis was focused on evaluating the correlation between glycemic control and the restoration effect of glucokinase activator on β-cell function. Method: The analysis has involved two phase III clinical trials of dorzagliatin, monotherapy (SEED) (NCT03173391) and metformin add-on (DAWN) (NCT03141073) , respectively. The change of HOMA2-IR, IGI and DI from baseline to 24 weeks were analyzed. Correlation between glycemic control status and patient’s early phase insulin secretion ability as well as glucose sensitivity were further demonstrated by logistic regression analysis with IGI, DI, HOMA2-IR and other characteristics. Results: Totally 726 patients were included in the final analysis set, with 241 patients from SEED cohort and 485 patients from DAWN. After 24 weeks treatment, two cohorts showed the consistent result of IGI and DI improvement. Nevertheless, The improvement of IGI and DI for HbA1c controlled group (HbA1c <7%) were significantly higher than HbA1c uncontrolled group (HbA1c ≥ 7%) . The result was also consistent across different disease course groups in DAWN cohort considering the relatively longer disease course. Logistic regression analysis revealed that both the improvement of IGI and DI were independent influential factor of patient’s HbA1c controlled status after treatment of dorzagliatin. Conclusion: The post hoc analysis demonstrated the beneficial effect of dorzagliatin on early insulin secretion ability and glucose sensitivity on T2DM patients. The HbA1c control status were significantly affected by improvement of early insulin secretion ability and glucose sensitivity both for drug naïve patients and metformin tolerated patient. Disclosure L. Feng: Employee; Hua Medicine. Q. Guo: None. C. Chen: Employee; Hua Medicine. X. Liu: Employee; Hua Medicine. L. Chen: Employee; Hua Medicine. W. Yang: Advisory Panel; Hua Medicine. Funding Hua Medicine