title: Efficacy and Safety of Canagliflozin Used in Conjunction with Sulfonylurea in Patients with Type 2 Diabetes Mellitus: A Randomized, Controlled Trial.
abstract: BACKGROUND
  The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on sulfonylurea monotherapy.
  
  
  METHODS
  The CANagliflozin cardioVascular Assessment Study (CANVAS) is a double-blind, placebo-controlled cardiovascular outcomes study that randomized participants to placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy. Participants in the CANVAS trial are men and women aged ≥30 years with T2DM and a history or high risk of cardiovascular disease, and inadequate glycemic control (glycated hemoglobin [HbA1c] ≥7.0% and ≤10.5%) on current antihyperglycemic therapies. The primary objective of this prespecified substudy was to assess change from baseline to 18 weeks in HbA1c among patients on sulfonylurea monotherapy.
  
  
  RESULTS
  Of the 4330 patients enrolled in CANVAS, 127 met the entry criteria for the sulfonylurea monotherapy substudy (placebo, n = 45; canagliflozin 100 mg, n = 42; canagliflozin 300 mg, n = 40). At 18 weeks, placebo-subtracted changes (95% confidence interval) in HbA1c were -0.74% (-1.15, -0.33; P < 0.001) and -0.83% (-1.24, -0.42; P < 0.001) with canagliflozin 100 and 300 mg, respectively. Relative to placebo, canagliflozin 100 and 300 mg also decreased fasting plasma glucose (FPG; -2.1 mmol/L [-3.0, -1.2] and -2.7 mmol/L [-3.6, -1.7], respectively). Body weight was lower with canagliflozin 300 mg (-1.8% [-3.2, -0.4]; P = 0.014) but unchanged with canagliflozin 100 mg (-0.4% [-1.8, 1.0]; P = 0.557). Canagliflozin 300 mg increased hypoglycemia episodes compared to canagliflozin 100 mg and placebo (15%, 0%, and 4.4%, respectively). Adverse events (AEs) of male and female genital mycotic infections, pollakiuria, and thirst were more common with canagliflozin.
  
  
  CONCLUSIONS
  Canagliflozin added to ongoing sulfonylurea monotherapy produced improvements in HbA1c, FPG, and body weight, with an increased incidence of AEs consistent with the mechanism of action of SGLT2 inhibition.
  
  
  BACKGROUND
  Janssen Research & Development, LLC.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01032629.
authors.affiliation: The Royal North Shore Hospital and University of Sydney, Sydney, Australia. greg.fulcher@sydney.edu.au.
authors.forename: Greg
authors.initials: G
authors.lastname: Fulcher
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Matthews
authors.affiliation: The George Institute for Global Health, The University of Sydney and the Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Zeeuw
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Maine Research Associates, Auburn, ME, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Weiss
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: George
authors.initials: G
authors.lastname: Capuano
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Mehul
authors.initials: M
authors.lastname: Desai
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Shaw
authors.affiliation: Janssen Research & Development, Beerse, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Vercruysse
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Meininger
authors.affiliation: The George Institute for Global Health, The University of Sydney and the Royal Prince Alfred Hospital, Sydney, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
keywords: Canagliflozin; Cardiovascular disease; SGLT2 inhibitor; Sulfonylureas; Type 2 diabetes