A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity

This is a phase 1, open-label, single-sequence, multiple-dose, single-center trial conducted in the US (NCT03790839), to evaluate the clinical pharmacokinetics, safety and pharmacodynamics of dorzagliatin co-administered with sitagliptin in patients with T2D and obesity. The trial has completed. 15 patients with T2D and obesity were recruited and treated with sitagliptin 100mg QD on Day 1-5, followed by a combination of sitagliptin 100mg QD with dorzagliatin 75mg BID at second stage on Day 6-10 and the third stage of dorzagliatin 75mg BID alone on Day 11-15. Primary outcomes include pharmacokinetic geometric mean ratio (GMR), safety and tolerability. Secondary outcomes include the incremental area under the curve for 4hours post oral glucose tolerance test (iAUC) of pharmacodynamic biomarkers and glucose sensitivity. GMR for AUC(0-24h) and C-max were 92.63 (90% CI, 85.61, 100.22) and 98.14 (90% CI, 83.73, 115.03) in combination/sitagliptin, and 100.34 (90% CI, 96.08, 104.79) and 102.34 (90% CI, 86.92, 120.50) in combination/dorzagliatin, respectively. Combination treatment did not increase the adverse events and well-tolerated in T2D patients. Lack of clinically meaningful pharmacokinetic interactions between dorzagliatin and sitagliptin, and an improvement of glycemic control under combination potentially support their co-administration for diabetes management. Dorzagliatin, which acts on the glucose sensor glucokinase, is a new class of anti-diabetic medicine. Here the authors report that in a phase I open-label trial co-administration of dorzagliatin and sitagliptin (a different class of anti-diabetic medicine) does not significantly change the pharmacokinetics of either medicine in patients with type 2 diabetes and obesity.