Journal of Diabetes Research & Clinical Metabolism

Journal of Diabetes Research & Clinical
Metabolism

ISSN 2050-0866
Original Research

Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, and Glimepiride Following Co-administration in Healthy Volunteers: A Randomised, Open-label, Crossover Study

Sreeraj Macha1*, Michaela Mattheus2, Sabine Pinnetti3, Leo Seman1 and Hans J. Woerle2

*Corresponding author: Sreeraj Macha sreeraj.macha@boehringer-ingelheim.com

1. Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA


Author Affiliations

2. Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, Ingelheim 55216, Germany

3. Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach 88397, Germany

Abstract

Background: Empagliflozin is a potent and selective sodium glucose cotransporter 2 inhibitor in development for the treatment of type 2 diabetes mellitus. This randomised open-label crossover study investigated potential drug–drug interactions between empagliflozin and the sulphonylurea glimepiride.

Methods: Sixteen healthy male volunteers received 3 treatments (A: 50 mg qd empagliflozin for 5 days, B: 50 mg empagliflozin and 1 mg glimepiride for 1 day, C: 1 mg glimepiride for 1 day) in one of two treatment sequences (AB then C, or C then AB). A washout period of ≥7 days separated treatments AB and C.

Results: Co-administration of glimepiride with empagliflozin had no clinically relevant effects on the area under the plasma concentration-time curve (AUCτ,ss geometric mean ratio [GMR] 95.2; 90% CI: 92.0, 98.5) or the maximum plasma concentration (Cmax,ss GMR 95.6; 90% CI: 88.2, 103.5) for empagliflozin or for glimepiride (AUC0-∞ GMR 93.3; 90% CI: 86.1, 101.0; Cmax GMR 104.2; 90% CI: 89.5, 121.3). Five subjects (31.3%) reported at least one adverse event (AE). Headache (18.8%) was the most frequently reported AE (1 subject while taking empagliflozin and 2 subjects while taking glimepiride). No hypoglycaemia was reported. All AEs were mild or moderate.

Conclusions: Co-administration of empagliflozin and glimepiride did not alter the pharmacokinetics of either drug and was well tolerated. These data suggest that empagliflozin can be co-administered with glimepiride without dose adjustment of either drug.

Trial registration: European Union Drug Regulating Authorities Clinical Trials Eudra CT2008-006060-11

Keywords: Type 2 diabetes, empagliflozin, BI 10773, SGL T2 inhibitor, glimepiride, drug–drug interaction

ISSN 2050-0866
Volume 1
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