title: Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes mellitus inadequately controlled on metformin and sitagliptin.
abstract: To evaluate the efficacy and safety of titrated canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and sitagliptin.
  
  
  
  In this randomized, double-blind study, patients with T2DM (N = 218) on metformin ≥1500 mg/day and sitagliptin 100 mg received canagliflozin 100 mg or placebo. After 6 weeks, the canagliflozin dose was increased from 100 to 300 mg (or from placebo to matching placebo) if all of the following criteria were met: baseline estimated glomerular filtration rate ≥70 ml/min/1.73 m(2) ; fasting self-monitored blood glucose ≥5.6 mmol/l (≥100 mg/dl); and no volume depletion-related adverse events (AEs) within 2 weeks before dose increase. Endpoints included change in glycated haemoglobin (HbA1c) at week 26 (primary); proportion of patients achieving HbA1c <7.0%; and changes in fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP). Safety was assessed using AE reports.
  
  
  
  Overall, 85.4% of patients were titrated to canagliflozin 300 mg or matching placebo (mean ± standard deviation time to titration 6.2 ± 0.8 weeks). At week 26, canagliflozin (pooled 100 and 300 mg) demonstrated superiority in HbA1c reduction versus placebo (-0.91% vs. -0.01%; p < 0.001). Canagliflozin provided significant reductions in FPG, body weight and SBP compared with placebo (p < 0.001). The overall AE incidence was 39.8 and 44.4% for canagliflozin and placebo, respectively. Canagliflozin was associated with an increased incidence of genital mycotic infections.
  
  
  
  Titrated canagliflozin significantly improved HbA1c, FPG, body weight and SBP, and was generally well tolerated over 26 weeks in patients with T2DM as add-on to metformin and sitagliptin.
authors.affiliation: Endocrine and Metabolic Consultants, Rockville, MD, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Rodbard
authors.affiliation: Department of Endocrinology and Diabetology, Clinic for Internal Medicine II, University Medical Center, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Seufert
authors.affiliation: Aggarwal and Associates Ltd, Brampton, ON, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Aggarwal
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cao
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Fung
authors.affiliation: Janssen Scientific Affairs, LLC, Raritan, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Pfeifer
authors.affiliation: Janssen Research & Development, LLC, Raritan, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Alba
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D000068896:Canagliflozin / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D020896:Hypovolemia / Q000139:chemically induced; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009181:Mycoses / Q000139:chemically induced; D060737:Reproductive Tract Infections / Q000139:chemically induced; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000139:chemically induced
chemical_list: D001786:Blood Glucose; D000068896:Canagliflozin; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000068900:Sitagliptin Phosphate; C517652:hemoglobin A1c protein, human
keywords: canagliflozin; sitagliptin; sodium glucose co-transporter; titration; triple therapy; type 2 diabetes mellitus