Evogliptin is a newly developed oral glucose-lowering medication of the dipeptidyl peptidase 4 (DPP-4) inhibitor class for type 2 diabetes mellitus. The combination of a DPP-4 inhibitor with pioglitazone is a promising therapeutic option. The aim of the present study was to evaluate the pharmacokinetic and pharmacodynamic interaction between evogliptin and pioglitazone.
A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence crossover study was conducted in healthy Korean male subjects. All subjects received evogliptin 5 mg once daily for 7 days (EVO), pioglitazone 30 mg once daily for 7 days (PIO) and co-administration of evogliptin 5 mg and pioglitazone 30 mg once daily for 7 days (EVO+PIO) according to the assigned sequence and period. Serial blood samples were collected for 24 hours for pharmacokinetic analysis and 3 hours after the oral glucose tolerance test for the pharmacodynamic analysis.
Thirty-four subjects completed the study. EVO+PIO and EVO showed a similar maximum plasma concentration at steady state (C max,ss) and area under the concentration-time curve during the dosing interval at the steady state (AUC τ,ss) of evogliptin, with geometric mean ratios (GMRs) (90% confidence interval (CI)) of 1.01 (0.97–1.05) and 1.01 (0.98–1.04), respectively. EVO+PIO and PIO showed a similar C max,ss and AUC τ,ss of pioglitazone, with GMRs (90% CI) of 1.07 (0.99–1.17) and 1.08 (0.99–1.17), respectively. Reduction of the glucose level after EVO+PIO was larger compared to PIO and similar with EVO.