title: Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study.
abstract: OBJECTIVE
  To compare the pharmacodynamic effects of the highest approved doses of the sodium glucose co-transporter 2 (SGLT2) inhibitors canagliflozin and dapagliflozin on urinary glucose excretion (UGE), renal threshold for glucose excretion (RTG ) and postprandial plasma glucose (PPG) excursion in healthy participants in a randomized, double-blind, two-period crossover study.
  
  
  METHODS
  In each treatment period, participants (n = 54) received canagliflozin 300 mg or dapagliflozin 10 mg for 4 days (20 min before breakfast). A mixed-meal tolerance test (600 kcal; 75 g glucose) was performed at baseline and on day 4 of each treatment period to assess changes in incremental PPG (PPGΔAUC0-2 h ). We measured 24-h UGE and plasma glucose on day 4 to determine 24-h mean RTG .
  
  
  RESULTS
  Canagliflozin 300 mg and dapagliflozin 10 mg had similar effects on UGE and RTG for 4 h after dosing, but canagliflozin was associated with higher UGE and greater RTG reductions for the remainder of the day. Mean 24-h UGE was ∼25% higher with canagliflozin than with dapagliflozin (51.4 vs. 40.8 g), and 24-h mean RTG was ∼0.4 mmol/l (7 mg/dl) lower with canagliflozin than with dapagliflozin (3.79 vs. 4.17 mmol/l; p < 0.0001). Dapagliflozin had no effect on PPG excursion; canagliflozin delayed and reduced PPG excursion (between-treatment difference in PPGΔAUC0-2 h from baseline expressed as a percentage of baseline mean, -10.2%; p = 0.0122). Canagliflozin and dapagliflozin were generally well tolerated.
  
  
  CONCLUSIONS
  In healthy participants, canagliflozin 300 mg provided greater 24-h UGE, a lower RTG and smaller PPG excursions than dapagliflozin 10 mg.
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sha
authors.forename: D
authors.initials: D
authors.lastname: Polidori
authors.forename: K
authors.initials: K
authors.lastname: Farrell
authors.forename: A
authors.initials: A
authors.lastname: Ghosh
authors.forename: J
authors.initials: J
authors.lastname: Natarajan
authors.forename: N
authors.initials: N
authors.lastname: Vaccaro
authors.forename: J
authors.initials: J
authors.lastname: Pinheiro
authors.forename: P
authors.initials: P
authors.lastname: Rothenberg
authors.forename: L
authors.initials: L
authors.lastname: Plum-Mörschel
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight; D000068896:Canagliflozin; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D013876:Thiophenes / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D013876:Thiophenes; D000068896:Canagliflozin; C529054:dapagliflozin; D005947:Glucose
keywords: SGLT2 inhibitor; canagliflozin; dapagliflozin; pharmacodynamics; phase I-II study; type 2 diabetes