Efficacy and safety of canagliflozin in patients with type 2 diabetes A meta-analysis of randomized controlled trials

Background: Canagliflozin is a new SGLT2 inhibitor which has been approved as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes (T2D) mellitus in more than 30 countries. To evaluate the efficacy and safety of canagliflozin in patients with T2D, we carried out a meta-analysis of phase III clinical trials to offer an additional evidence of the efficacy and safety of canagliflozin for evidence-based clinical practice, strictly restricting the treatment durations to 26 weeks (core period) and 52 weeks (extension period). Methods: Randomized controlled trials (RCTs) published in English were searched in PubMed, Embase, and the Cochrane Library database (before April 2016). The studies reporting the efficacy and safety of canagliflozin in patients with T2DM were considered. Two authors separately performed data extraction. The differences were discussed and resolved. Pooled weighted mean differences (WMDs) or relative risks and 95% confidence intervals (CIs) were computed by using either fixed- or random-effects models. Results: At the end of the selection process, 7 RCTs were collected and included in the present analysis. Placebo-subtracted WMDs (%) of glycosylated hemoglobin (HbA1c) were -0.63 (95% CI: -0.77, -0.49) and -0.80 (95% CI: -0.98. -0.62) for canagliflozin 100 and 300 mg, respectively, from baseline to week 26. At week 26, canagliflozin 100 and 300 mg significantly reduced the body weight from baseline when compared with that of placebo, with a WMD of -2.23 and -3.00 in percent changes (P < 0.001 for both). The fasting and postmeal glucose, blood pressure (BP), and triglycerides were also reduced. These reductions were sustained over 52 weeks but had no significant differences between the 100 and 300 mg doses. The overall safety of canagliflozin was good, with the exception of high incidence of genital mycotic infections and osmotic diuresis-related adverse events. Conclusion: Canagliflozin was found to reduce HbA1c, fasting and postmeal glucose, body weight, BP, and triglycerides, and it was generally well tolerated in patients with T2DM.