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Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double‐blind, crossover study
Author(s) -
Sha S.,
Polidori D.,
Farrell K.,
Ghosh A.,
Natarajan J.,
Vaccaro N.,
Pinheiro J.,
Rothenberg P.,
PlumMörschel L.
Publication year - 2015
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12418
Subject(s) - canagliflozin , dapagliflozin , crossover study , medicine , pharmacodynamics , endocrinology , excretion , postprandial , pharmacokinetics , type 2 diabetes , urology , chemistry , placebo , diabetes mellitus , alternative medicine , pathology
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 ( RT G ) 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 ( PPGΔAUC 0–2 h ). We measured 24‐h UGE and plasma glucose on day 4 to determine 24‐h mean RT G . Results Canagliflozin 300 mg and dapagliflozin 10 mg had similar effects on UGE and RT G for 4 h after dosing, but canagliflozin was associated with higher UGE and greater RT G 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 RT G 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 PPGΔAUC 0–2 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 RT G and smaller PPG excursions than dapagliflozin 10 mg.