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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.

Author(s): Stein P(1), Berg JK(2), Morrow L(3), Polidori D(4), Artis E(1), Rusch S(5), Vaccaro N(6), Devineni D(1).

Affiliation(s): Author information: (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. Electronic address: DPolido1@its.jnj.com. (5)Janssen Research & Development, Beerse, Belgium. (6)Janssen Research & Development, LLC, San Diego, CA, USA.

Publication date & source: 2014, Metabolism. , 63(10):1296-303

OBJECTIVE: Canagliflozin 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/METHODS: Patients (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. RESULTS: A 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. CONCLUSIONS: These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg.

Page last updated: 2014-11-30

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