No Drug–Drug Interaction between Dorzagliatin and Metformin in Type 2 Diabetes Patients

Dorzagliatin (HMS5552) is a new glucokinase activator and showed excellent antidiabetic effects in type 2 diabetes (T2D) patients with good tolerability. It is in Phase 3 clinical development for a new oral antidiabetic drug. Drug-drug interaction (DDI) potential between dorzagliatin and Metformin was investigated in an open-label clinical study in Chinese T2D patients. T2D subjects (n=15) in general good health between 18 and 70 years old, BMI of 22 to 38 kg/m2, fasting C-peptide >0.3 nmol/L, and HbA1c 7% to 12% were randomized in the study. They had been diagnosed of T2D for at least 3 months and were taking a stable daily dose of ≥1000 mg of Metformin for at least 4 weeks. All subjects were standardized to Metformin 500 mg BID for at least two weeks prior to study day 1. In the study, subjects were treated with Metformin (500 mg BID) on days 1-2 and a morning dose only on day 3 before PK samples were collected for 24 hours. On days 4-7, subjects were treated with Metformin (500 mg BID) and dorzagliatin (50 mg BID), and day 8 morning a single dose of each drug was given before PK samplings. Subjects were then treated with dorzagliatin (50 mg BID) on days 9-12, a single dose only on day 13 morning, and followed by PK samplings. Pharmacodynamic (PD) parameters (glucose, insulin and C-peptide levels) were evaluated on days 3, 8 and 13. Study results demonstrated that Metformin had no effect on the exposure of dorzagliatin (Cmax and AUC0-t). The AUC0-t of Metformin remained unchange when co-administered with dorzagliatin while the Cmax was slightly lower than Metformin alone. It is concluded that there was no significant DDI between dorzagliatin and Metformin. Dose adjustment is not warranted when they are co-administered. PK/PD analysis suggested that co-administration of dorzagliatin and Metformin compared to each drug alone can further improve glycemic control in T2D patients. Both drugs were well tolerated in the study. Disclosure L. Chen: None. G. Zhao: None. S. Ren: None. Y. Zhang: None. D. Du: None.