A Safety and Efficacy Study of Canagliflozin in Older Patients (55 to 80 Years of Age) With Type 2 Diabetes Mellitus

• Change in hemoglobin A1c from Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
  

• Change in fasting plasma glucose from Baseline to Week 26 [ Time Frame: Day 1 (Baseline) to Week 26 ] [ Designated as safety issue: No ]
  
• Percent change in body weight from Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
  
• Change in total fat from Baseline to Week 26 in a subset of patients undergoing specific dual-energy X-ray absorptiometry analysis for body composition [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
  
• Change in region percent total fat from Baseline to Week 26 in a subset of patients undergoing specific dual-energy X-ray absorptiometry analysis for body composition [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
  
• Change in tissue percent total fat from Baseline to Week 26 in a subset of patients undergoing specific dual-energy X-ray absorptiometry analysis for body composition [ Time Frame: Day 1 (Baseline) to Week 26 ] [ Designated as safety issue: No ]
  
• Change in systolic blood pressure from Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
  
• Percent change in triglycerides from Baseline to Week 26 [ Time Frame: Day 1 (Baseline) to Week 26 ] [ Designated as safety issue: No ]
  
• Percent change in high-density lipoprotein cholesterol (HDL-C) from Baseline to Week 26 [ Time Frame: Day 1 (Baseline) and Week 26 ] [ Designated as safety issue: No ]
  
• Percentage of patients with hemoglobin A1c <7% [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
  
• Percent change in lumbar spine bone mineral density from Baseline to Week 26 [ Time Frame: Day 1 (Baseline) to Week 26 ] [ Designated as safety issue: Yes ]
  

Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient or the study doctor will know the name of the assigned treatment), placebo-controlled, parallel-group, 3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy to control their diabetes. Approximately 720 older (55 to 80 years of age) patients with T2DM who are either not on an antihyperglycemic agent or who are receiving treatment with a stable regimen of antihyperglycemic agent(s) and have inadequate glycemic (blood sugar) control will receive once daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 104 weeks (includes 26 weeks of double-blind treatment followed by a 78-week extension period). In addition, all patients will take stable doses of the antihyperglycemic agent(s) that they were taking before entry in the study for the duration of the study. Patients will participate in the study for approximately 108 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with an antihyperglycemic agent (rescue therapy) that is considered clinically appropriate and consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, measures of bone health, 12-lead electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. All patients will take single-blind placebo capsules for 2 weeks before randomization. After randomization, patients will take double blind canagliflozin (100 mg or 300 mg) or matching placebo for 104 weeks.