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

AimsTo 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. MethodsIn each treatment period, participants (n=54) received canagliflozin 300mg or dapagliflozin 10mg for 4days (20min before breakfast). A mixed-meal tolerance test (600kcal; 75g glucose) was performed at baseline and on day 4 of each treatment period to assess changes in incremental PPG (PPGAUC(0-2 h)). We measured 24-h UGE and plasma glucose on day 4 to determine 24-h mean RTG. ResultsCanagliflozin 300mg and dapagliflozin 10mg had similar effects on UGE and RTG for 4h after dosing, but canagliflozin was associated with higher UGE and greater RTG reductions for the remainder of the day. Mean 24-h UGE was approximate to 25% higher with canagliflozin than with dapagliflozin (51.4 vs. 40.8g), and 24-h mean RTG was approximate to 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 PPGAUC(0-2 h) from baseline expressed as a percentage of baseline mean, -10.2%; p=0.0122). Canagliflozin and dapagliflozin were generally well tolerated. ConclusionsIn healthy participants, canagliflozin 300mg provided greater 24-h UGE, a lower RTG and smaller PPG excursions than dapagliflozin 10mg.