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

• Published in: Diabetes, obesity & metabolism Vol. 17; no. 2; pp. 188 - 197
• Main Authors: Sha, S., Polidori, D., Farrell, K., Ghosh, A., Natarajan, J., Vaccaro, N., Pinheiro, J., Rothenberg, P., Plum-Mörschel, L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2015; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Antidiabetics; Benzhydryl Compounds - pharmacokinetics; Benzhydryl Compounds - therapeutic use; Blood Glucose - drug effects; Body Weight; Canagliflozin; Cross-Over Studies; dapagliflozin; Diabetes; Double-Blind Method; Drug Administration Schedule; Drug therapy; Excretion; Female; Glomerular Filtration Rate; Glucose; Glucose - metabolism; Glucose transporter; Glucosides - pharmacokinetics; Glucosides - therapeutic use; Humans; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - therapeutic use; Kidney - metabolism; Male; Middle Aged; Original; Pharmacodynamics; phase I-II study; Postprandial Period; Renal function; SGLT2 inhibitor; Thiophenes - pharmacokinetics; Thiophenes - therapeutic use; type 2 diabetes; phase I-II study; type 2 diabetes; SGLT2 inhibitor; dapagliflozin; pharmacodynamics; canagliflozin
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12418

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.