Effects Of SGLT-2 Inhibitors Combined With Insulin In Diabetes On Risk Factors Of Cardiovascular Disease: A Meta-analysis Of Randomized Controlled Trials

Objective:We aimed to determine the effects of using SGLT-2i in combination with insulin when adding or not adding other oral antidiabetic drugs on risk factors of cardiovascular disease in type 1 and 2 diabetes patients.Methods:Randomized controlled trials(RCTs)were identified by searching the Pubmed,Embase,and Cochrane Library databases for studies Published before September 2017.Two authors independently performed the data extraction by eligibility criteria and data extraction.Differences were resolved in discussions or by the third reviewer.We assessed pooled data,including weighted mean differences(WMDs)and 95%confidence intervals(CIs),using random-effects or fixed-effects models.P<0.1 were considered heterogeneous and I~2>50%were moderately and highly heterogeneous.The sensitivity of the results was analyzed,and the publication bias was evaluated by funnel plot.Results:Our initial search strategy identified 2890 citations.Of these,thirteen randomized controlled trials(n=6072 participants)were eligible.The placebo-subtracted WMDs for systolic blood pressure and diastolic blood pressure were-3.09mmhg and-1.48mmhg for the intervention groups.Glycosylated hemoglobin(HbA1c)levels,fasting plasma glucose(FPG)levels,postprandial glucose(PPG)levels and daily insulin(IU/d)were also lower in the intervention groups,with relative WMDs of-0.47%,-0.96mmol/l,-3.63mmol/land-5.46IU/d.The transformations in body weight and uric acid were-2.32kg and-26.16μmol/L when compared with placebo groups.Compared with the control group,hypoglycemia and hyperglycemia(including hyPerglycemia ketoacidosis)relative risk was 1.13(P<0.05)and 1.78(P<0.05),urinary tract infection and reproductive tract infection increased relative risk was 1.46(P<0.05)and 3.87(P<0.05)and SGLT-2 inhibitor group compared with the control group,no significant difference between severe hypoglycemia(P>0.05).Conclusions:The results showed that in the intervention group,greater reductions were achieved in SBP,DBP,and uric acid and daily insulin levels when patients were treated with an SGLT-2i combined with insulin±OADs.This treatment regimen may therefore provide beneficial effects that reduce the occurrence and development of cardiovascular events.