title: Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial.
abstract: BACKGROUND
  Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). Our randomized, double-blind, placebo-controlled, phase 3 study (www.clinicaltrials.gov: NCT01106651) evaluated the efficacy and safety of canagliflozin therapy in older subjects (aged 55-80 years) with T2DM inadequately controlled on their current regimen of blood glucose-lowering agents (any approved oral or injectable treatment).
  
  
  METHODS
  Subjects (N = 716) aged 55 to 80 years (mean, 63.6 years) with glycated hemoglobin (HbA1c) levels ≥ 7.0% to ≤ 10.0% were randomized. Seven hundred fourteen received canagliflozin 100 mg or 300 mg or placebo (1:1:1) daily. The prespecified primary endpoint was change from baseline in HbA1c level at week 26. Prespecified secondary endpoints included proportion of subjects achieving HbA1c levels < 7.0%, change from baseline in fasting plasma glucose (FPG) level and systolic blood pressure (BP), and percent change from baseline in body weight, triglyceride levels, and high-density lipoprotein cholesterol (HDL-C) level. Adverse events (AEs) were reported throughout the study.
  
  
  RESULTS
  At week 26, treatment with canagliflozin 100 mg and 300 mg significantly reduced HbA1c levels compared with placebo (-0.60%, -0.73%, -0.03%, respectively; P < 0.001); more subjects achieved HbA1c levels < 7.0% with both canagliflozin doses compared with placebo (P < 0.001). Both canagliflozin doses significantly reduced body weight, FPG level, and systolic BP, and increased HDL-C level compared with placebo (P < 0.001); low-density lipoprotein cholesterol level was increased with both canagliflozin doses compared with placebo. The overall AE incidence was slightly higher with canagliflozin 300 mg than with canagliflozin 100 mg or placebo (78.0%, 72.2%, 73.4%, respectively). Serious AE and AE-related discontinuation rates were low across groups. Both canagliflozin doses were associated with higher rates than placebo of genital mycotic infections, urinary tract infections, and osmotic diuresis-related AEs (ie, pollakiuria, polyuria). Documented hypoglycemia rates were modestly higher with both canagliflozin doses compared with placebo.
  
  
  CONCLUSIONS
  Canagliflozin improved glycemic control, reduced body weight and systolic BP, and was generally well tolerated in older subjects with T2DM who were on background therapy with a variety of blood glucose-lowering agents.
authors.affiliation: Atlanta Diabetes Associates, Atlanta, GA 30318, USA. bbode001@aol.com
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
authors.forename: Kaj
authors.initials: K
authors.lastname: Stenlöf
authors.forename: Daniel
authors.initials: D
authors.lastname: Sullivan
authors.forename: Albert
authors.initials: A
authors.lastname: Fung
authors.forename: Keith
authors.initials: K
authors.lastname: Usiskin
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005960:Glucosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012449:Safety; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin