CANagliflozin Treatment And Trial Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride

Type 2 diabetes mellitus (T2DM) is well recognized as a major public health problem that presents patients with a significant risk of complications including heart disease, retinopathy, nephropathy, and neuropathy. Various classes of orally administered antihyperglycemic agents have been developed for the treatment of diabetes and although individual agents may be highly effective for some patients, it is still difficult to maintain optimal glycemic control in most patients, thereby resulting in high rates of morbidity and mortality in the diabetic population. This is a randomized, double-blind, active comparator-controlled, 3-arm, parallel-group, multicenter study to demonstrate the efficacy, safety, and tolerability of canagliflozin compared with a sulfonylurea (glimepiride) in patients with T2DM, 18 to 80 years of age, inclusive, who are not optimally controlled on metformin monotherapy. The primary study hypothesis is that the study drug will be non-inferior to glimepiride as assessed by the change in hemoglobin A1c (HbA1c) from baseline. The patients will receive capsules taken by mouth of canagliflozin (either 100 or 300 mg), or glimepiride with a starting dosage of 1 mg, which will be increased to a maximum dose of 6 or 8 mg once daily for a total duration of 104 weeks.

Inclusion criteria

• Patients must have a diagnosis of type 2 diabetes
• Body mass index (BMI) >=22 to <=45 kg/m2, at screening
• Patients must be taking a stable dosage of metformin as monotherapy at screening
• Patients must have a HbA1c between >=7% and <=9.5% at Week 2
• Patients must have a fasting plasma glucose (FPG) <=270 mg/dL (15 mmol/L) at Week -2

Exclusion criteria

• Patients having prior exposure or known contraindication or suspected hypersensitivity to JNJ-28431754, glimepiride, or metformin
• History of diabetic ketoacidosis or type 1 diabetes mellitus
• History of pancreas or beta-cell transplantation
• History of active proliferative diabetic retinopathy
• History of hereditary glucose-galactose malabsorption or primary renal glucosuria
• Renal disease requiring treatment with immunosuppressive therapy within the past 12 months before screening or a history of dialysis or renal transplant
• Taken thiazolidinedione therapy in the past 16 weeks before screening