Sglt2Inhibitor-Canagliflozin For Type2Diabetes: A Systematic Review

Objective: To assess efficacy and safety of the novel SGLT2inhibitor—canagliflozin for type2diabetes （T2DM）. Methods: Wesearched Pubmed, EMBASE, Highwire, the Cochrane Library, highwire, CBM,CNKI, Wanfang, VIP Database and literature from some relative paper basedmagazines also be retrieved. Randomised controlled trials （RCTs） ofcanagliflozin compared to placebo or active comparator in T2DM were selected.Select the RCTs according to the inclusion criterion, then appraise themcritiically by Cochrane handbook. All outcomes were pooled by the RevMan5.2software of Cochrane Collaboration. Result:9randomized, double–blind,controlled trials involving6432patients with T2DM were analyzed. Thepublished language of included trials was English and trial durations rangedfrom12to52weeks. The meta–analysis indicated that:①Compared withplacebo, canagliflozin provided higher reduction in HbA1c [WMD=–0.79,95%CI（–0.88,–0.69）, P<0.00001], there was no statistically significantdifference in HbA1c when compared canagliflozin with sitagliptin[WMD=–0.15,95%CI（–0.30,–0.00）, P=0.05].②Compared with placebo orsitagliptin, canagliflozin provide a significant greater reduction in FPG[WMD=–32.51,95%CI（–35.52,–29.50）, P<0.00001; WMD=–15.35,95%CI（–21.56,–9.14）, P<0.00001].③Compared with placebo or sitagliptin,canagliflozin lead to greater body weight loss [WMD=–2.43,95%CI（–2.77, –2.08）, P<0.00001; WMD=–2.67,95%CI（–2.96,–2.38）, P<0.00001].④Therisk of hypoglycaemia in canagliflozin were similar with placebo or sitagliptin[RR=1.35,95%C（I0.68,2.71）, P=0.39; RR=1.34,95%C（I0.94,1.92）, P=0.11].⑤Compared with placebo or sitagliptin, canagliflozin lead to no higher risk ofurinary tract infections [RR=1.21,95%CI（0.92,1.61）, P=0.18; RR=1.14,95%CI（0.82,1.58）, P=0.44]; the risk of genital tract infections were higherwith canagliflozin [RR=3.29,95%C（I2.01,5.40）, P<0.00001; RR=4.20,95%CI（2.77,6.36）, P<0.0001]. Conclusions:①Treatment with canagliflozinprovided clinically important and statistically significant improvements inHbA1c levels as well as FPG levels in patients with T2DM.②Canagliflozinwere associated with statistically significant improvements body weight.③Therisk of genital infections are higher with canagliflozin, the risk of hypoglycemiaand urinary tract infections are lower.④Longer and larger observation isneeded to understand the comparative benefits and risks of canagliflozin andthe durability of response.