Objective: The oral minimal model (OMM) is a powerful tool to assess beta-cell function, including both the dynamic and static states. Dorzagliatin, a novel dual-acting glucokinase activator, has been reported the potential to improve pancreatic function in patients with type-2 diabetes mellitus (T2DM). In this study, we aimed to evaluate the effects of dorzagliatin on beta-cell function by using OMM.
Methods: A randomized, double-blind, placebo-controlled study of dorzagliatin following multiple ascending doses in T2DM was completed (NCT02077452) and the data collected were used for beta-cell function parameters (Φb, Φd, Φs, and Φtot) estimation by using the SAAM II package integrating OMM. These parameters represent the non-glucose stimulated index, the dynamic responsivity of insulin secretion, the static responsivity of insulin secretion, and the global index of beta-cell responsivity, respectively.
Results: All treatments except for the 200 mg dose group, compared with baseline, were associated with higher beta-cell function indices. Among them, Φb was significantly higher in the 25, 50, 100, and 150 mg dose groups (p < 0.05, p < 0.01, or p < 0.001), indicating basal beta-cell responsivity improved. Φd has an increase in the 25 and 100 mg dose groups (p < 0.05), indicating promptly releasable insulin responsivity improved. Φs was higher in the 25, 50, 100, and 150 mg dose groups (p < 0.05 or p < 0.01), indicating insulin secretion responsivity at steady state improved. Φtot significantly increased in the 25, 50, 100, and 150 mg dose groups (p < 0.05 or p < 0.001), indicating total beta-cell responsivity improved. No statistically significant difference was observed within the placebo group.
Conclusions: This study suggested dorzagliatin can improve postprandial glucose control through its positive effects on beta-cell function.
Y. Zhang: None. L. Feng: Employee; Hua Medicine. L. Chen: Employee; Hua Medicine. D. Liu: None.
