| Objective To assess efficacy and safety of the novel sodium glucose transporter2(SGLT2) inhibitor in T2DM.Methode According to purpose of this systematic review, the appropriate inclusion criteria (including the type of research, participant, intervention, outcome) and detailed search strategy were conducted in accordance with the method of Cochrane systematic reviews. We searched Keywords and the MeSH joint free word respectively, according to the characteristics of different databases, without language restrictions. We searched PubMed, EMBASE, the Cochrane Library, The National Reseach Register, Highwire, ISI, CBM, CNKI, WANFANG Database, VIP and at the same time hand searched from1998to2013relevant journals, as well as retrieved relevant documents on the Internet by such as Google search engine, from inception to March2013. Two reviewers independently screened the studies for eligibility, extracted the data from the eligible studies, with the confirmation of cross-check. Different opinions would be decided by the third party. According to criteria for judging risk of bias in the ’Risk of bias’ assessment tool of Handbook of Cochrane Review Manager5.1software, the risk of bias of included trials such as random sequence generation(selection bias), allocation concealment(selection bias), blinding of participants and personnel(performance bias), blingding of outcome assessment(detection bias), incomplete outcome data(attrition bias), selective reporting(reporting bias) and other bias was assessed. Statistical analysis was performed by the RevMan5.1software of Cochrane Collaboration. The heterogeneity would be analyzed before Pooling data. After heterogeneity test, data without heterogeneity (p>0.1,12<50%) could be pooled using fixed effect model, and those with heterogeneity (p<0.1, I2>50%) could be solved by sensitivity analysis, subgroup analysis as well as randomized effect model. We will compare outcome measures for dichotomous(binary) data using relative risks(RR) and continuous data using standardized mean difference(SMD) with95%confidence intervals(CI). A two-sided P<0.05was considered significant. We will describe the outcomes when the data cannot be pooled or the raw data of outcomes cannot be acquired. The funnel plot will be use to assess bias of publication. We will evaluate the quality of this systematic review by using the GRADE Proflier3.6software.Results Eleven randomized, double-blind, controlled trials involving3151patients with type2diabetes mellitus were included. There was a cross-over trial. The published language of included trials was English. The included trials period was ranged from12days to52weeks. The agents of SGLT2inhibitors that included in the study, were Dapagliflozin, Canagliflozin, Remogliflozin etabonate and Ipragliflozin (ASP1941). The meta-analysis results of effectiveness indicated that the SGLT2inhibitors produced more effective than placebo in decreasing HbAlc[P<0.00001, SMD=-3.55,95%CI (-4.30,-2.80)]and fasting plasma glucose[P<0.00001, SMD=-2.86,95%CI (-3.52,-2.20)]. There was no significant differences in reduction of HbAlc[P=0.78, SMD=-0.10,95%CI (-0.85,0.64)] and fasting plasma glucose[P=0.05, SMD=-1.34,95%CI (-2.68,0.00)] between the SGLT2inhibitors group and other oral antidiabetic drugs group. The SGLT2inhibitors group, in incidence of adverse events, was higher to placebo[P=0.02, RR=1.07,95%CI (1.01,1.13)], was similar to other oral antidiabetic drugs[P=0.52, RR=0.98,95%CI (0.92,1.04)]. Compared with placebo group and other oral antidiabetic drugs, no significant differences was observed regarding the occurrence of serious adverse events, hypoglycemic events and urinary tract infections in SGLT2inhibitor (P>0.05). In incidence of genital infections, SGLT2inhibitors group more than placebo[P<0.00001, RR=3.36,95%CI (2.32,4.86)] and other oral antidiabetic drugs[P<0.00001, RR=3.89,95%CI(2.27,6.67)]. SGLT2inhibitors significantly decreased the body weight, compared with placebo[P<0.00001, SMD=-1.18,95%CI (-1.55,-0.82)] and other oral antidiabetic drugs[P<0.00001, SMD=-0.46,95%CI (-0.63,-0.29)]. In blood pressure, the systolic blood pressure of the SGLT2inhibitors group decreased significantly compared to placebo[P<0.00001, SMD=-1.47,95%CI(-2.02,-0.92)] and other oral hypoglycemic agents group[P<0.001, SMD=-0.28,95%CI (-0.44,-0.11)]. The SGLT2inhibitors group showed more effective in the drop in diastolic blood pressure between placebo group[P<0.0001, SMD=-1.15,95%CI (-1.70,-0.60)], similar to other oral hypoglycemic agents group[P=0.80, SMD=0.02,95%CI (-0.14,0.19)]. The results of GRADE profliler indicated that the SGLT 2inhibitors group, compared with placebo group, the outcomes of HbAlc and changes in body weight were HIGH quality, the outcomes of fasting blood glucose, serious adverse events, hypoglycemic events, systolic blood pressure, urinary tract infections were MODERATE quality, the outcomes of adverse events, diastolic blood pressure, genital infections were LOW quality. Between the SGLT2inhibitors and other oral hypoglycemic agents, the GRADEprofliler showed that the outcomes of changes in body weight was HIGH quality, the outcomes of fasting blood glucose, adverse events, serious adverse events were MODERATE quality, the outcomes of diastolic blood pressure changes, systolic blood pressure changes, hypoglycemic events, urinary tract infection, genital infections were LOW quality:, the outcomes of HbAlc was VERY LOW quality.Conclusions①The SGLT2inhibitors can effectively reduce HbAlc and fasting blood glucose.②The incidence of SGLT2inhibitors adverse events is relatively lower, and the risk of hypoglycemia and urinary tract infections are lower, but the risk of genital infections are higher.③The SGLT2inhibitors can reduce body weight, and has antihypertensive effect.④Since there are some limitations, we expect that future systematic review could involve more high quality evidences provided by high quality double-blind randomized control trials to assess efficacy and safety of the SGLT2inhibitors in T2DM. |
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