title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Stein
authors.affiliation: DaVita Clinical Research, Minneapolis, MN, USA.
authors.forename: Jolene K
authors.initials: JK
authors.lastname: Berg
authors.affiliation: Profil Institute for Clinical Research, Inc., Chula Vista, CA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Morrow
authors.affiliation: Janssen Research & Development, LLC, San Diego, CA, USA. Electronic address: DPolido1@its.jnj.com.
authors.forename: David
authors.initials: D
authors.lastname: Polidori
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Eunice
authors.initials: E
authors.lastname: Artis
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rusch
authors.affiliation: Janssen Research & Development, LLC, San Diego, CA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Vaccaro
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Damayanthi
authors.initials: D
authors.lastname: Devineni
mesh_terms: D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D000068896:Canagliflozin; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin; D008687:Metformin; D005947:Glucose
keywords: Mixed-meal tolerance test; Postprandial glucose excursion; Urinary glucose excretion