Improvement of early‐phase insulin secretion is an independent factor for achieving glycaemic control: A pooled analysis of SEED and DAWN study

Abstract Aim To investigate the effect of improving early phase insulin secretion function for glycaemic control in patients with type 2 diabetes mellitus treated with a new class of antidiabetic drug dorzagliatin. Materials and Methods Early insulin secretion function was studied in 726 participants of which 414 were treated with dorzagliatin in the SEED and DAWN study. The early insulinogenic index (IGI 30min ) and disposition index (DI) were used to assess early‐phase insulin secretion function in this study. Logistic regression analysis was performed to verify the importance of IGI 30min and DI indices for achieving effective glycaemic control. Results The reduction in HbA1c has a significant correlation with the improvement of IGI 30min for patients that received 24 weeks of dorzagliatin treatment ( p < .001), and this correlation was not observed in the placebo group ( p = .364). In the dorzagliatin treatment group, the responders showed significant improvements in homeostasis model assessment 2‐β, IGI 30min and DI compared with the non‐responders. Logistic regression analysis revealed that the odds ratio (OR) for achieving glycaemic control was 1.28 (95% CI 1.14‐1.43) for baseline IGI 30min , and 1.24 (95% CI 1.14‐1.35) for the 24‐week incremental IGI 30min from baseline. The OR for baseline DI and 24‐week changes in DI from baseline were 1.39 (95% CI 1.2‐1.6) and 1.30 (95% CI 1.19‐1.43) respectively. The timing of insulin secretion analysis showed the significant contribution of early‐phase insulin secretion, rather than late‐phase insulin secretion, to postprandial glucose control with the OR for the incremental IGI 30min and IGI 2h to postprandial glucose control were 1.3 (95% CI 1.19‐1.42) and 1 (95% CI 1‐1.01) respectively. Conclusions Restoring the impaired early‐phase insulin secretion function in patients with type 2 diabetes mellitus is a critical factor for improving the glycaemic control by dorzagliatin treatment.