Effects Of SGLT-2 Inhibitors On Macrovascular Risk Factors In Type 2 Diabetes:a Systematic Review

Objective To evaluate the effects of SGLT-2 inhibitors on macrovascular risk factors in type 2 diabetes mellitus and provide a theoretical basis to select antidiabetic drugs.Methods The following databases as PubMed,EMBASE, Cochrane Library, China National Knowledge (CNKI), WanFang,VIP,Chinese Biomedical Literature Database (CBM) data(deadline to March,2015)were searched to collect the randomized controlled trials (RCTs) of SGLT-2 inhibitors vs placebo in effects of SGLT-2 inhibitors on macrovascular risk factors with type 2 diabetes mellitus.It is assessed the quality in accordance with the Cochrane Handbook 5.1 and conducted meta-analyses with RevMan 5.2 software.We will compare outcome measures for dichotomous(binary) data using relative risks(RR) and continuous data using standardized mean difference(SMD) with 95% confidence intervals(CI) and P value. Data without heterogeneity (p≥ 0.1,12≤ 50%) could be pooled using fixed effect model, and those with heterogeneity (p<0.1,12>50%) could be solved by subgroup analysis. We will describe the outcomes when the data cannot be pooled or the raw data of outcomes cannot be acquired.A two-sided P<0.05 was considered significant. The funnel plot will be use to assess bias of publication.Results A total of 15 prospective randomized, double-blind,controlled trials involving 5220 patients with T2DM which SGLT-2 inhibitors group 3393 cases,1827 cases in the control group were analyzed.The published language of included trials was English and trial durations ranged from 12 to 52 weeks. The results of systematic review showed that:①SGLT-2 inhibitors produced more effective than placebo in decreasing HbAlc[SMD=-0.94,95%CI (-1.14,-0.74),P< 0.00001].It is with statistical heterogeneity between studies (P< 0.00001,I2=90%).Subgroup analyses showed that short or long duration,short-term or long-term treatment,combined medication or not of SGLT-2 inhibitors lead to more reduction in HbAlc than placebo.②SGLT-2 inhibitors significantly decreased the body weight[SMD=-0.72,95%CI (-0.88,-0.55),P<0.00001].③SGLT-2 inhibitors provide a greater reduction in systolic blood pressure [SMD=-0.32,95% CI (-0.38,-0.26),P< 0.00001], and diastolic blood pressure [SMD=-0.28,95%CI (-0.34,-0.21),P<0.00001].④GLT-2 inhibitors provide a greater reduction in triglycerides [SMD=-0.17,95%CI (-0.23,-0.11),P<0.00001]; Treatment with SGLT-2 inhibitors was associated with a significant increase in high-density lipoprotein cholesterol levels[SMD=0.30,95% CI (0.21,0.38),P< 0.00001]; there is a certain increased risk of low-density lipoprotein cholesterol levels[SMD=0.17,95%CI (0.11,0.23),P<0.00001].Conclusions SGLT-2 inhibitors can effectively reduce HbAlc,body weight,blood pressure as well as triglycerides, and increase high-density lipoprotein cholesterol levels in patients with T2DM, However, there is a certain increased risk of low-density lipoprotein cholesterol levels.