Canagliflozin: Effects in Overweight and Obese Subjects Without Diabetes Mellitus

Objective: To evaluate the effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on body weight in overweight and obese subjects (body mass index [BMI] >= 27 and < 50 kg/ m(2)). Methods: This 12-week, Phase 2b, randomized, double-blind study enrolled 376 subjects without diabetes mellitus who received canagliflozin 50, 100, or 300 mg or placebo once daily. The primary endpoint was the percent change in body weight from baseline through Week 12. Results: Canagliflozin increased urinary glucose excretion in a dose-dependent manner and produced statistically significant reductions in body weight compared with placebo (least squares mean percent changes from baseline of -22.2%, -22.9%, -22.7%, and -21.3% with canagliflozin 50, 100, and 300 mg and placebo; P<0.05 for all comparisons). Overall adverse event (AE) rates were similar across groups. Canagliflozin was associated with higher rates of genital mycotic infections in women, which were generally mild and led to few study discontinuations. Osmotic diuresis-related AE rates were low and similar across groups. Conclusions: In overweight and obese subjects without diabetes mellitus, canagliflozin significantly reduced body weight compared with placebo and was generally well tolerated.