title: Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  The purpose of this study was to assess the effect of renal impairment on the pharmacokinetic, pharmacodynamic, and safety profiles of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  In an open-label, parallel-group study, 32 Japanese patients with T2DM and different degrees of renal function (n = 8 per renal function category: normal renal function, estimated glomerular filtration rate [eGFR; Japanese equation] ≥90 mL/min/1.73 m(2); mild renal impairment, eGFR of 60-<90 mL/min/1.73 m(2); moderate renal impairment, eGFR of 30-<60 mL/min/1.73 m(2); and severe renal impairment, eGFR of 15-<30 mL/min/1.73 m(2)) received a single 25 mg dose of empagliflozin.
  
  
  RESULTS
  Empagliflozin exposure increased with increasing renal impairment. Maximum empagliflozin plasma concentrations were similar among all renal function groups. Adjusted geometric mean ratios for extent of exposure (AUC0-∞) to empagliflozin versus normal renal function were 128.8% (95% CI, 106.0-156.6%), 143.8% (95% CI, 118.3-174.8%), and 152.3% (95% CI, 125.3-185.2%) for patients with mild, moderate, and severe renal impairment, respectively. Decreases in renal clearance of empagliflozin correlated with eGFR. Urinary glucose excretion decreased with increasing renal impairment and correlated with eGFR (adjusted mean [SE] change from baseline: 75.0 [4.84] g, 62.6 [5.75] g, 57.9 [4.86] g, and 23.7 [5.24] g for patients with normal renal function and mild, moderate, and severe renal impairment, respectively). Only 2 patients (6%) had adverse events; both were mild.
  
  
  CONCLUSIONS
  Pharmacokinetic data suggest that no dose adjustment of empagliflozin is necessary in Japanese patients with T2DM and renal impairment because increases in exposure were <2-fold. Urinary glucose excretion decreased with increasing renal impairment. ClinicalTrials.gov identifier: NCT01581658.
authors.affiliation: Nippon Boehringer Ingelheim Co Ltd, Hyogo, Japan. Electronic address: akiko.sarashina@boehringer-ingelheim.com.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sarashina
authors.affiliation: Department of Molecular Sciences on Diabetes, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Molecular Diabetic Medicine, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Kohjiro
authors.initials: K
authors.lastname: Ueki
authors.affiliation: Nippon Boehringer Ingelheim Co Ltd, Hyogo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Nippon Boehringer Ingelheim Co Ltd, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Nippon Boehringer Ingelheim Co Ltd, Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Koiwai
authors.affiliation: Nippon Boehringer Ingelheim Co Ltd, Tokyo, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakamoto
authors.affiliation: Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.
authors.forename: Afshin
authors.initials: A
authors.lastname: Salsali
authors.affiliation: Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.
authors.forename: Sreeraj
authors.initials: S
authors.lastname: Macha
mesh_terms: D000368:Aged; D044466:Asian People; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D005919:Glomerular Filtration Rate; D005960:Glucosides / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin
keywords: Japanese patients; SGLT2 inhibitor; empagliflozin; pharmacodynamics; pharmacokinetics; renal impairment