Canagliflozin,a sodium glucose co-transporter 2 inhibitor,reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial |
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Authors: | Peter Stein Jolene K Berg Linda Morrow David Polidori Eunice Artis Sarah Rusch Nicole Vaccaro Damayanthi Devineni |
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Affiliation: | 1. Janssen Research & Development, LLC, Raritan, NJ, USA;2. DaVita Clinical Research, Minneapolis, MN, USA;3. Profil Institute for Clinical Research, Inc., Chula Vista, CA, USA;4. Janssen Research & Development, LLC, San Diego, CA, USA;5. Janssen Research & Development, Beerse, Belgium |
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Abstract: | ObjectiveCanagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin.Materials/MethodsPatients (N = 37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion UGE] expected for Treatments B–D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period.ResultsA single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B–D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC0–2h, − 7.5% for B vs A; − 18.5% for C vs A; − 12.0% P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC0–2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated.ConclusionsThese findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg. |
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Keywords: | AE adverse event AUC area under the concentration-time curve BMI body mass index C150 canagliflozin 150 mg C300 canagliflozin 300 mg CI confidence interval CRC clinical research center CV coefficient of variation FPG fasting plasma glucose LS least squares MET metformin MMTT mixed-meal tolerance test NA not applicable PBO placebo PG plasma glucose ΔPG incremental plasma glucose SD standard deviation SE standard error SGLT1 sodium glucose co-transporter 1 SGLT2 sodium glucose co-transporter 2 SU sulfonylurea UGE urinary glucose excretion |
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