Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study

Diabetes Obes Metab. 2015 Feb;17(2):188-97. doi: 10.1111/dom.12418. Epub 2015 Jan 5.

Abstract

Aims: 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.

Keywords: SGLT2 inhibitor; canagliflozin; dapagliflozin; pharmacodynamics; phase I-II study; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / pharmacokinetics*
  • Benzhydryl Compounds / therapeutic use
  • Blood Glucose / drug effects*
  • Body Weight
  • Canagliflozin
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Glomerular Filtration Rate
  • Glucose / metabolism*
  • Glucosides / pharmacokinetics*
  • Glucosides / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use
  • Kidney / metabolism*
  • Male
  • Middle Aged
  • Postprandial Period
  • Thiophenes / pharmacokinetics*
  • Thiophenes / therapeutic use

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Hypoglycemic Agents
  • Thiophenes
  • Canagliflozin
  • Glucose