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/m2). Methods: This 12-week, Phase 2b, randomized, double-blind study enrolled 376 subjects without diabe-tes 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. Canagli-flozin 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