title: Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial.
abstract: OBJECTIVE
  Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind, placebo-controlled, Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM.
  
  
  METHODS
  Patients (N = 469) received canagliflozin 100 or 300 mg or placebo once daily during a 26-week core period and a 26-week extension. Prespecified primary end-point was change in HbA1c at 26 weeks. Secondary end-points included change in HbA1c at week 52 as well as proportion of patients achieving HbA1c < 7.0%, change in fasting plasma glucose (FPG) and systolic blood pressure, and per cent change in body weight, high-density lipoprotein cholesterol, and triglycerides (weeks 26 and 52).
  
  
  RESULTS
  HbA1c was significantly reduced with canagliflozin 100 and 300 mg vs. placebo at week 26 (-0.85%, -1.06%, and -0.13%; p < 0.001); these reductions were maintained at week 52 (-0.74%, -0.96%, and 0.01%). Both canagliflozin doses reduced FPG and body weight vs. placebo at week 26 (p < 0.001) and week 52. Overall adverse event (AE) rates were similar across groups over 52 weeks, with higher rates of genital mycotic infections and osmotic diuresis-related AEs seen with canagliflozin vs. placebo; these led to few discontinuations. Increased incidence of documented, but not severe, hypoglycaemia episodes was seen with canagliflozin vs. placebo.
  
  
  CONCLUSIONS
  Canagliflozin improved glycaemic control, reduced body weight, and was generally well tolerated in T2DM patients on metformin plus sulphonylurea over 52 weeks.
authors.affiliation: Department of Obesity and Endocrinology, University of Liverpool, Liverpool, UK.
authors.forename: J P H
authors.initials: JP
authors.lastname: Wilding
authors.forename: G
authors.initials: G
authors.lastname: Charpentier
authors.forename: P
authors.initials: P
authors.lastname: Hollander
authors.forename: G
authors.initials: G
authors.lastname: González-Gálvez
authors.forename: C
authors.initials: C
authors.lastname: Mathieu
authors.forename: F
authors.initials: F
authors.lastname: Vercruysse
authors.forename: K
authors.initials: K
authors.lastname: Usiskin
authors.forename: G
authors.initials: G
authors.lastname: Law
authors.forename: S
authors.initials: S
authors.lastname: Black
authors.forename: W
authors.initials: W
authors.lastname: Canovatchel
authors.forename: G
authors.initials: G
authors.lastname: Meininger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D050417:Insulin-Secreting Cells / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D000068896:Canagliflozin; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds; D013876:Thiophenes