Efficacy and safety of canagliflozin rnonotherapy in Japanese patients with type 2 diabetes inadequately controlled with diet and exercise: a 24-week, randomized, double-blind, placebo-controlled, Phase III study

Objective: To examine the efficacy and safety of canagliflozin monotherapy, a sodium/glucose co-transporter 2 inhibitor, in Japanese type 2 diabetes patients. Methods: In this double-blind, multi-centre Phase III study, patients aged 20 years with hemoglobin A1c (HbA1c) 7.0 - 10.0% on diet/exercise therapy alone received placebo or canagliflozin (100 or 200 mg) once daily for 24 weeks. The main outcome measure was the change in HbA1c from baseline to Week 24. Results: The changes in HbA1c (-0.74 and -0.76 vs + 0.29%), fasting plasma glucose (1 mg/dl = 0.0555 mmol/l; -31.6 and -31.9 vs + 3.7 mg/dl), 2-h plasma glucose after 75-g glucose load (-84.9 and -79.0 vs -0.5 mg/dl), body weight (percent change: -3.76 and -4.02 vs -0.76%) and systolic blood pressure (-7.88 and -6.24 vs -2.72 mmHg) were significantly greater with 100 and 200 mg canagliflozin than with placebo (all, p<0.05). Genital infections in females (6.5, 6.3 and 0%) and asymptomatic hypoglycemia (4.4, 5.6 and 2.2%), but not symptomatic hypoglycemia (2.2, 1.1 and 1.1%), were more frequent in the 100- and 200-mg groups than in the placebo group. Conclusion: Canagliflozin significantly improved glycemic control and was well tolerated.