Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial

AimsCanagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of type 2 diabetes mellitus (T2DM). This randomised, double-blind, placebo-controlled, Phase 3 study evaluated the efficacy and safety of canagliflozin as an add-on to metformin plus sulphonylurea in patients with T2DM. MethodsPatients (N=469) received canagliflozin 100 or 300mg or placebo once daily during a 26-week core period and a 26-week extension. Prespecified primary end-point was change in HbA(1c) at 26weeks. Secondary end-points included change in HbA(1c) at week 52 as well as proportion of patients achieving HbA(1c) <7.0%, change in fasting plasma glucose (FPG) and systolic blood pressure, and per cent change in body weight, high-density lipoprotein cholesterol, and triglycerides (weeks 26 and 52). ResultsHbA(1c) was significantly reduced with canagliflozin 100 and 300mg vs. placebo at week 26 (-0.85%, -1.06%, and -0.13%; p<0.001); these reductions were maintained at week 52 (-0.74%, -0.96%, and 0.01%). Both canagliflozin doses reduced FPG and body weight vs. placebo at week 26 (p<0.001) and week 52. Overall adverse event (AE) rates were similar across groups over 52weeks, with higher rates of genital mycotic infections and osmotic diuresis-related AEs seen with canagliflozin vs. placebo; these led to few discontinuations. Increased incidence of documented, but not severe, hypoglycaemia episodes was seen with canagliflozin vs. placebo. ConclusionsCanagliflozin improved glycaemic control, reduced body weight, and was generally well tolerated in T2DM patients on metformin plus sulphonylurea over 52weeks.