Pharmacokinetic/Pharmacodynamic Interactions Between Evogliptin and Glimepiride in Healthy Male Subjects

Abstract

Purpose

Evogliptin, a dipeptidyl peptidase-4 inhibitor, and glimepiride, a sulfonylurea, are used to treat type 2 diabetes mellitus. In this study, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride.

Materials and 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 a combination of the two (EVO+GLI). Serial blood and urine samples were collected 168 and 24 h post dosing, respectively, for PK and PD analyses.

Results

Thirty-four subjects completed the study. The 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 (C_max,ss) and the area under the curve during dosing interval at steady-state (AUC_τ,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 0.8–1.25. Glucose excursion decreased with the co-administration of evogliptin and glimepiride compared with that observed with the evogliptin or glimepiride monotherapy.

Conclusion

Evogliptin and glimepiride had no PK interactions when co-administered, while the combination therapy showed an additive glucose-lowering effect compared to those of evogliptin or glimepiride monotherapy.

Keywords:

• evogliptin
• glimepiride
• pharmacokinetics
• pharmacodynamics
• drug interaction

Acknowledgments

This study was sponsored by Dong-A ST Co., Ltd., Seoul, Republic of Korea.

Data Sharing Statements

The data that support the findings of this study are available from the corresponding investigator upon reasonable request.

Disclosure

The authors have no competing interests to declare.