Dorzagliatin (HMS5552), a Novel Dual Acting Glucokinase Activator, Improves Glycemic Control and Pancreatic β-cell Function in Patients with Type 2 Diabetes: A 28-day Treatment Study Using Biomarker-Guided Patient Selection.

Aims: To investigate the pharmacokinetics and pharmacodynamics of a dual-acting glucokinase activator, dorzagliatin, and its safety, tolerability and effect on pancreatic beta-cell function in Chinese patients with type 2 diabetes (T2D). Materials and methods: A total of 24 T2D patients were selected, utilizing a set of predefined clinical biomarkers, and were randomized to receive dorzagliatin 75 mg twice or once daily (BID, QD respectively) for 28 days. Changes in HbA1c and glycaemic parameters from baseline to Day 28 were assessed. In addition, changes in beta-cell function from baseline to Day 32 were evaluated. Results: Significant reductions in HbA1c were observed in both regimens on Day 28 (-0.79%, 75 mg BID; -1.22%, 75 mg QD). Similar trends were found in the following parameters, including reductions from baseline in fasting plasma glucose by 1.20 mmol/L and 1.51 mmol/L, in 2-hour postprandial glucose by 2.48 mmol/L and 5.03 mmol/L, and in glucose AUC(0-24) by 18.59% and 20.98%, for the BID and QD groups, respectively. Both regimens resulted in improvement in beta-cell function as measured by steady state HOMA 2 parameter, %B, which increased by 36.31% and 40.59%, and by dynamic state parameter, Delta C-30/Delta G(30), which increased by 24.66% and 167.67%, for the BID and QD groups, respectively. Dorzagliatin was well tolerated in both regimens, with good pharmacokinetic profiles. Conclusions: Dorzagliatin treatment for 28 days in Chinese T2D patients, selected according to predefined biomarkers, resulted in significant improvement in beta-cell function and glycaemic control. The safety and pharmacokinetic profile of dorzagliatin supports a subsequent Phase II trial design and continued clinical development.