Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double‐blind, crossover study. Issue 2 (5th January 2015)

• Record Type: Journal Article
• Authors: Sha, S.; Polidori, D.; Farrell, K.; Ghosh, A.; Natarajan, J.; Vaccaro, N.; Pinheiro, J.; Rothenberg, P.; Plum‐Mörschel, L.
• Is Part Of: Diabetes, obesity & metabolism. Volume 17:Issue 2(2015:Feb.)
• Page Start: 188
• Page End: 197
• Publication Date: 2015-01-05
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12418
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12418-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="dom12418-sec-0001" sec-type="section"> <title>Aims</title> <p id="dom12418-para-0001">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<sub>G</sub>) and postprandial plasma glucose (PPG) excursion in healthy participants in a randomized, double‐blind, two‐period crossover study.</p> </sec> <sec id="dom12418-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12418-para-0002">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<sub>0–2 h</sub>). We measured 24‐h UGE and plasma glucose on day 4 to determine 24‐h mean RT<sub>G</sub>.</p> </sec> <sec id="dom12418-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12418-para-0003">Canagliflozin 300 mg and dapagliflozin 10 mg had similar effects on UGE and RT<sub>G</sub> for 4 h after dosing, but canagliflozin was associated with higher UGE and greater RT<sub>G</sub> 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<sub>G</sub> 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<sub>0–2 h</sub> from baseline expressed as a percentage of baseline mean, −10.2%; p = 0.0122). Canagliflozin and dapagliflozin were generally well tolerated.</p> </sec> <sec id="dom12418-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12418-para-0004">In healthy participants, canagliflozin 300 mg provided greater 24‐h UGE, a lower RT<sub>G</sub> and smaller PPG excursions than dapagliflozin 10 mg.</p> </sec> </abstract>