Aims: Evogliptin is a newly developed oral glucose-lowering medication of dipeptidyl peptidase 4 (DPP-4) inhibitor class for type 2 diabetes mellitus. Combination of DPP-4 inhibitor with pioglitazone is a promising therapeutic option. The aim of present study was to evaluate pharmacokinetic and pharmacodynamic interaction between evogliptin and pioglitazone. Methods: 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 oral glucose tolerance test for pharmacodynamic analysis. Results: Thirty-four subjects completed the study. EVO+PIO and EVO showed similar maximum plasma concentration at steady state (Cmax,ss) and the area under the concentration-time curve during dosing interval at steady state (AUCτ,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 similar Cmax,ss and AUCτ,ss of pioglitazone, with GMRs (90% CI) of 1.07 (0.99-1.17) and 1.08 (0.99-1.17), respectively. Reduction of glucose level after EVO+PIO was larger compared to PIO, and similar with EVO. Conclusion: Concomitant administration of evogliptin and pioglitazone showed similar glucose lowering effects with those of evogliptin alone without pharmacokinetic interactions when compared to intake of each drug alone.

Aims: Evogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor and glimepiride, a sulfonylurea, have been used to treat type 2 diabetes mellitus. This study aimed at evaluating the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride. Methods: A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or co-administration of the two (EVO+GLI). Serial blood and urine samples for PK and PD analyses were collected 168 and 24 hours post-dosing, respectively. Results: Thirty-four subjects completed the study. Co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (Cmax,ss) and the area under the curve during dosing interval at steady-state (AUCτ,ss) of EVO+GLI to E were 1.02 (0.98 – 1.06) and 0.97 (0.95 – 1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01 – 1.17) and 1.08 (1.02 – 1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.80 – 1.25. Administration of EVO+GLI decreased the glucose excursion compared to evogliptin and glimepiride monotherapy, respectively. Conclusion: Evogliptin and glimepiride had no PK interactions when co-administered, while combination therapy showed an additive glucose lowering effect compared to those of evogliptin or glimepiride monotherapy.