title: Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, and metformin following co-administration in healthy volunteers.
abstract: OBJECTIVE
  This open-label study investigated potential drug-drug interactions between empagliflozin and metformin.
  
  
  METHODS
  16 healthy men received treatment A (empagliflozin 50 mg q.d. for 5 days), treatment B (empagliflozin 50 mg q.d. for 4 days with metformin 1,000 mg b.i.d. for 3 days and 1,000 mg q.d. on Day 4) and treatment C (metformin 1,000 mg b.i.d. for 3 days and 1,000 mg q.d .on Day 4) in the sequence AB then C, or C then AB.
  
  
  RESULTS
  Metformin had no clinically relevant effect on the area under the steady state plasma concentration-time curve (AUC(τ,ss) geometric mean ratio (GMR): 96.9; 90% CI: 92.3 - 101.7) or the maximum plasma concentration at steady state (C(max,ss) GMR: 100.5; 90% CI: 88.8 - 113.7) of empagliflozin. Similarly, empagliflozin had no clinically relevant effect on AUC(τ,ss) (GMR: 100.7; 90% CI: 95.9 - 105.6) or C(max,ss) (GMR: 103.6; 90% CI: 96.5 - 111.2) of metformin. The renal clearance of empagliflozin and metformin were unaffected by co-administration. Both drugs were well tolerated alone and in combination and did not cause hypoglycemia.
  
  
  CONCLUSIONS
  These data support co-administration of empagliflozin and metformin without dose adjustment.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. sreeraj.macha@boehringer-ingelheim.com
authors.forename: Sreeraj
authors.initials: S
authors.lastname: Macha
authors.forename: Sabine
authors.initials: S
authors.lastname: Dieterich
authors.forename: Michaela
authors.initials: M
authors.lastname: Mattheus
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Seman
authors.forename: Uli C
authors.initials: UC
authors.lastname: Broedl
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D005960:Glucosides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D012016:Reference Values; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D008687:Metformin; C570240:empagliflozin