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Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment.
Diabetes Obes Metab. 2014 Mar; 16(3):215-22.DO

Abstract

AIMS

Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus (T2DM).

METHODS

In this open-label study, the effect of renal impairment on the pharmacokinetics, pharmacodynamics and safety of a 50 mg dose of empagliflozin was investigated in 40 subjects, grouped according to estimated glomerular filtration rate (eGFR).

RESULTS

Maximum empagliflozin plasma concentrations were similar in subjects with normal renal function and renal impairment. Area under the empagliflozin concentration-time curve (AUC0 -∞) values increased by approximately 18, 20, 66 and 48% in subjects with mild, moderate, severe renal impairment and renal failure/end stage renal disease (ESRD), respectively, in comparison to healthy subjects. This was attributed to decreased renal clearance (CLR). Urinary glucose excretion (UGE) decreased with increasing renal impairment and correlated with decreased eGFR and CLR . Empagliflozin was well tolerated, with no increase in adverse events associated with renal impairment.

CONCLUSIONS

Renal insufficiency resulted in decreased CLR of empagliflozin, moderately increased systemic exposure and decreased UGE. A single 50 mg dose of empagliflozin was well tolerated in subjects with normal renal function and any degree of renal impairment. The pharmacokinetic results of this study indicate that no dose adjustment of empagliflozin is required in patients with renal impairment.

Authors+Show Affiliations

Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23859488

Citation

Macha, S, et al. "Pharmacokinetics, Pharmacodynamics and Safety of Empagliflozin, a Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor, in Subjects With Renal Impairment." Diabetes, Obesity & Metabolism, vol. 16, no. 3, 2014, pp. 215-22.
Macha S, Mattheus M, Halabi A, et al. Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes Obes Metab. 2014;16(3):215-22.
Macha, S., Mattheus, M., Halabi, A., Pinnetti, S., Woerle, H. J., & Broedl, U. C. (2014). Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. Diabetes, Obesity & Metabolism, 16(3), 215-22. https://doi.org/10.1111/dom.12182
Macha S, et al. Pharmacokinetics, Pharmacodynamics and Safety of Empagliflozin, a Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor, in Subjects With Renal Impairment. Diabetes Obes Metab. 2014;16(3):215-22. PubMed PMID: 23859488.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment. AU - Macha,S, AU - Mattheus,M, AU - Halabi,A, AU - Pinnetti,S, AU - Woerle,H J, AU - Broedl,U C, Y1 - 2013/08/19/ PY - 2013/04/08/received PY - 2013/05/13/revised PY - 2013/07/11/accepted PY - 2013/7/18/entrez PY - 2013/7/19/pubmed PY - 2014/11/18/medline KW - SGLT2 inhibitor KW - diabetes KW - empagliflozin KW - pharmacodynamics KW - pharmacokinetics KW - renal impairment SP - 215 EP - 22 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 16 IS - 3 N2 - AIMS: Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus (T2DM). METHODS: In this open-label study, the effect of renal impairment on the pharmacokinetics, pharmacodynamics and safety of a 50 mg dose of empagliflozin was investigated in 40 subjects, grouped according to estimated glomerular filtration rate (eGFR). RESULTS: Maximum empagliflozin plasma concentrations were similar in subjects with normal renal function and renal impairment. Area under the empagliflozin concentration-time curve (AUC0 -∞) values increased by approximately 18, 20, 66 and 48% in subjects with mild, moderate, severe renal impairment and renal failure/end stage renal disease (ESRD), respectively, in comparison to healthy subjects. This was attributed to decreased renal clearance (CLR). Urinary glucose excretion (UGE) decreased with increasing renal impairment and correlated with decreased eGFR and CLR . Empagliflozin was well tolerated, with no increase in adverse events associated with renal impairment. CONCLUSIONS: Renal insufficiency resulted in decreased CLR of empagliflozin, moderately increased systemic exposure and decreased UGE. A single 50 mg dose of empagliflozin was well tolerated in subjects with normal renal function and any degree of renal impairment. The pharmacokinetic results of this study indicate that no dose adjustment of empagliflozin is required in patients with renal impairment. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/23859488/Pharmacokinetics_pharmacodynamics_and_safety_of_empagliflozin_a_sodium_glucose_cotransporter_2__SGLT2__inhibitor_in_subjects_with_renal_impairment_ L2 - https://doi.org/10.1111/dom.12182 DB - PRIME DP - Unbound Medicine ER -