Dorzagliatin improves glucose-stimulated GLP-1 secretion in T2D and is synergistic with sitagliptin in glycemic control

Abstract

To evaluate the clinical pharmacokinetics and pharmacodynamics of dorzagliatin in glycemic control and glucose sensitivity alone or in combination with sitagliptin in obese T2D subjects. Fifteen obese T2D subjects were treated with sitagliptin 100 mg QD followed by a combination of sitagliptin 100 mg QD with dorzagliatin 75 mg BID at second stage and the third stage of dorzagliatin 75 mg BID alone. Together with improvement in early-phase insulin secretion, an additional 30% glucose-lowering effect was observed in combination (dorzagliatin + sitagliptin) in glucose iAUC0 − 4h. A significant increase of iCmax of glucose-stimulated GLP-1 secretion (GLP-1total) was observed in dorzagliatin monotherapy. The pharmacokinetic GMRs (AUC0 − 24h and Cmax) of dorzagliatin and sitagliptin for combination/either monotherapy fell within 80% -125%. Dorzagliatin regulates glucose-stimulated GLP-1 release and synergizes with sitagliptin in optimizing glycemic control in obese T2D patients. Lack of clinically meaningful pharmacokinetic interactions between dorzagliatin and sitagliptin supports their oral co-administration for diabetes management.