Efficacy and Safety of Canagliflozin as Add-On Therapy to Metformin in Type 2 Diabetes

Comparison of canagliflozin versus glimepiride (study A): Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, Balis DA, Canovatchel W, Meininger G: Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382:941–950, 2013.Comparison of canagliflozin versus placebo and sitagliptin (study B): Lavalle-Gonzalez FJ, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W, Meininger G: Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 56:2582–2592, 2013.Objectives. To evaluate the safety and efficacy of canagliflozin compared to glimepiride (study A) and placebo and sitagliptin (study B) in adults with type 2 diabetes with inadequate glycemic control on metformin monotherapy.Design and methods. Study A: Adults with type 2 diabetes inadequately controlled with metformin were randomized to canagliflozin, 100 mg ( n = 478) or 300 mg ( n = 474), or glimepiride, uptitrated to 6 or 8 mg/day once daily ( n = 473), all in combination with metformin. The primary efficacy endpoint was change in A1C after 52 weeks. The primary hypothesis was the noninferiority of canagliflozin, 100 or 300 mg or both, to glimepiride for A1C reduction at week 52.Study B: Adults with type 2 diabetes inadequately controlled with metformin were randomized to canagliflozin, 100 mg ( n = 368) or 300 mg ( n = 367); sitagliptin, 100 mg ( n = 366); or placebo ( n = 183) once daily for 26 weeks, all in combination with metformin. After 26 weeks, placebo-treated patients were switched to sitagliptin 100 mg; other patients continued on the same therapy for an additional 26 weeks. The primary efficacy endpoint was change in A1C after 26 weeks. …