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.
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