PMID- 25110280
OWN - NLM
STAT- MEDLINE
DCOM- 20141114
LR  - 20181202
IS  - 1532-8600 (Electronic)
IS  - 0026-0495 (Linking)
VI  - 63
IP  - 10
DP  - 2014 Oct
TI  - 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.
PG  - 1296-303
LID - S0026-0495(14)00198-X [pii]
LID - 10.1016/j.metabol.2014.07.003 [doi]
AB  - 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.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Stein, Peter
AU  - Stein P
AD  - Janssen Research & Development, LLC, Raritan, NJ, USA.
FAU - Berg, Jolene K
AU  - Berg JK
AD  - DaVita Clinical Research, Minneapolis, MN, USA.
FAU - Morrow, Linda
AU  - Morrow L
AD  - Profil Institute for Clinical Research, Inc., Chula Vista, CA, USA.
FAU - Polidori, David
AU  - Polidori D
AD  - Janssen Research & Development, LLC, San Diego, CA, USA. Electronic address: 
      DPolido1@its.jnj.com.
FAU - Artis, Eunice
AU  - Artis E
AD  - Janssen Research & Development, LLC, Raritan, NJ, USA.
FAU - Rusch, Sarah
AU  - Rusch S
AD  - Janssen Research & Development, Beerse, Belgium.
FAU - Vaccaro, Nicole
AU  - Vaccaro N
AD  - Janssen Research & Development, LLC, San Diego, CA, USA.
FAU - Devineni, Damayanthi
AU  - Devineni D
AD  - Janssen Research & Development, LLC, Raritan, NJ, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01381887
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140709
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Blood Glucose)
RN  - 0 (Glucosides)
RN  - 0 (SLC5A2 protein, human)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0 (Thiophenes)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 9100L32L2N (Metformin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Blood Glucose/*drug effects/metabolism
MH  - Canagliflozin
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Fasting/blood/metabolism
MH  - Female
MH  - Glucose/*metabolism
MH  - Glucosides/*therapeutic use
MH  - Humans
MH  - Kidney/drug effects/*metabolism
MH  - Male
MH  - Metformin/therapeutic use
MH  - Middle Aged
MH  - Postprandial Period/drug effects
MH  - Sodium-Glucose Transporter 2/metabolism
MH  - *Sodium-Glucose Transporter 2 Inhibitors
MH  - Thiophenes/*therapeutic use
OTO - NOTNLM
OT  - Mixed-meal tolerance test
OT  - Postprandial glucose excursion
OT  - Urinary glucose excretion
EDAT- 2014/08/12 06:00
MHDA- 2014/11/15 06:00
CRDT- 2014/08/12 06:00
PHST- 2014/03/12 00:00 [received]
PHST- 2014/06/10 00:00 [revised]
PHST- 2014/07/01 00:00 [accepted]
PHST- 2014/08/12 06:00 [entrez]
PHST- 2014/08/12 06:00 [pubmed]
PHST- 2014/11/15 06:00 [medline]
AID - S0026-0495(14)00198-X [pii]
AID - 10.1016/j.metabol.2014.07.003 [doi]
PST - ppublish
SO  - Metabolism. 2014 Oct;63(10):1296-303. doi: 10.1016/j.metabol.2014.07.003. Epub 
      2014 Jul 9.