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Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, coadministered with sitagliptin in healthy volunteers.
Adv Ther. 2012 Oct; 29(10):889-99.AT

Abstract

INTRODUCTION

This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion. Sitagliptin lowers blood glucose through an insulin-dependent mechanism of action.

METHODS

Sixteen healthy male volunteers received three treatments (A, B, C) in one of two treatment sequences (AB then C, or C then AB). In treatment AB, 50 mg empagliflozin was administered once daily (q.d.) for 5 days (treatment A), immediately followed by coadministration of 50 mg empagliflozin q.d. and 100 mg sitagliptin q.d. over 5 days (treatment B). In treatment C, 100 mg sitagliptin was administered q.d. for 5 days. A washout period of ≥7 days separated treatments AB and C.

RESULTS

Coadministration of sitagliptin with empagliflozin did not have a clinically relevant effect on the area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUC(τ,ss)) (geometric mean ratio [GMR] 110.4; 90% confidence interval [CI] 103.9, 117.3) or maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (C (max,ss)) (GMR 107.6; 90% CI 97.0, 119.4) of empagliflozin. Coadministration of empagliflozin with sitagliptin did not have a clinically meaningful effect on the AUC(τ,ss) (GMR 103.1; 90% CI 98.9, 107.3) or C (max,ss) (GMR 108.5; 90% CI 100.7, 116.9) of sitagliptin. Empagliflozin and sitagliptin were well tolerated when given alone or in combination. Five subjects (31.3%) reported at least one adverse event (AE): three (18.8%) experienced an AE while receiving empagliflozin monotherapy and three (18.8%) while receiving sitagliptin monotherapy. No adverse events were reported during the coadministration period. No AEs were regarded as drug-related by the investigator.

CONCLUSION

These results indicate that empagliflozin and sitagliptin can be coadministered without dose adjustments.

Authors+Show Affiliations

Department of Translational Medicine, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach, 88397, Germany. tobias.brand@boehringer-ingelheim.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23054692

Citation

Brand, Tobias, et al. "Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor, Coadministered With Sitagliptin in Healthy Volunteers." Advances in Therapy, vol. 29, no. 10, 2012, pp. 889-99.
Brand T, Macha S, Mattheus M, et al. Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, coadministered with sitagliptin in healthy volunteers. Adv Ther. 2012;29(10):889-99.
Brand, T., Macha, S., Mattheus, M., Pinnetti, S., & Woerle, H. J. (2012). Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, coadministered with sitagliptin in healthy volunteers. Advances in Therapy, 29(10), 889-99. https://doi.org/10.1007/s12325-012-0055-3
Brand T, et al. Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitor, Coadministered With Sitagliptin in Healthy Volunteers. Adv Ther. 2012;29(10):889-99. PubMed PMID: 23054692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT-2) inhibitor, coadministered with sitagliptin in healthy volunteers. AU - Brand,Tobias, AU - Macha,Sreeraj, AU - Mattheus,Michaela, AU - Pinnetti,Sabine, AU - Woerle,Hans J, Y1 - 2012/10/01/ PY - 2012/07/05/received PY - 2012/10/12/entrez PY - 2012/10/12/pubmed PY - 2013/11/13/medline SP - 889 EP - 99 JF - Advances in therapy JO - Adv Ther VL - 29 IS - 10 N2 - INTRODUCTION: This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion. Sitagliptin lowers blood glucose through an insulin-dependent mechanism of action. METHODS: Sixteen healthy male volunteers received three treatments (A, B, C) in one of two treatment sequences (AB then C, or C then AB). In treatment AB, 50 mg empagliflozin was administered once daily (q.d.) for 5 days (treatment A), immediately followed by coadministration of 50 mg empagliflozin q.d. and 100 mg sitagliptin q.d. over 5 days (treatment B). In treatment C, 100 mg sitagliptin was administered q.d. for 5 days. A washout period of ≥7 days separated treatments AB and C. RESULTS: Coadministration of sitagliptin with empagliflozin did not have a clinically relevant effect on the area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUC(τ,ss)) (geometric mean ratio [GMR] 110.4; 90% confidence interval [CI] 103.9, 117.3) or maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (C (max,ss)) (GMR 107.6; 90% CI 97.0, 119.4) of empagliflozin. Coadministration of empagliflozin with sitagliptin did not have a clinically meaningful effect on the AUC(τ,ss) (GMR 103.1; 90% CI 98.9, 107.3) or C (max,ss) (GMR 108.5; 90% CI 100.7, 116.9) of sitagliptin. Empagliflozin and sitagliptin were well tolerated when given alone or in combination. Five subjects (31.3%) reported at least one adverse event (AE): three (18.8%) experienced an AE while receiving empagliflozin monotherapy and three (18.8%) while receiving sitagliptin monotherapy. No adverse events were reported during the coadministration period. No AEs were regarded as drug-related by the investigator. CONCLUSION: These results indicate that empagliflozin and sitagliptin can be coadministered without dose adjustments. SN - 1865-8652 UR - https://www.unboundmedicine.com/medline/citation/23054692/Pharmacokinetics_of_empagliflozin_a_sodium_glucose_cotransporter_2__SGLT_2__inhibitor_coadministered_with_sitagliptin_in_healthy_volunteers_ L2 - https://dx.doi.org/10.1007/s12325-012-0055-3 DB - PRIME DP - Unbound Medicine ER -