title: Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment.
abstract: OBJECTIVE
  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.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.
authors.forename: S
authors.initials: S
authors.lastname: Macha
authors.forename: M
authors.initials: M
authors.lastname: Mattheus
authors.forename: A
authors.initials: A
authors.lastname: Halabi
authors.forename: S
authors.initials: S
authors.lastname: Pinnetti
authors.forename: H J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: U C
authors.initials: UC
authors.lastname: Broedl
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005215:Fasting; D005260:Female; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D016896:Treatment Outcome
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin; D005947:Glucose
keywords: SGLT2 inhibitor; diabetes; empagliflozin; pharmacodynamics; pharmacokinetics; renal impairment