Systematic Evaluation And Meta-analysis Of SGLT-2 Inhibitors Combined With Insulin In The Treatment Of Type 1 Diabetes

Objective:Sodium-dependent glucose transporters 2(SGLT-2)inhibitors are a novel drug for the treatment of type 2 diabetes.For now,there are many clinical studies that have shown the SGLT-2 inhibitors can be used for treating of the type 1 diabetes,but mixed results.The objective of this paper is systematically evaluated and meta analyzed about the efficacy and safety of SGLT-2 inhibitors combined with insulin used for the treatment of type 1diabetes,so that we can provide a theoretical basis which formulates a hypoglycemic program for T1DM.Methods:Until on 5th January,2019,searched on the registration websites of"pubmed","embase","cochrane Library","CNKI","Wanfang Database"and"Clicaltrials.gov",there has randomized controlled study that SGLT-2inhibitors is used for the treatment of type 1 diabetes.Acc ording to the inclusion and excluding criteria,after independently screened the literature,extracted the data and evaluated the quality,meta-analysis is studied with RevMan 5.3 software by two researchers.Results:A total of 6425 patients were enrolled in 13 randomized controlled trials.Glycated hemoglobin was reduced in the SGLT-2 inhibitor group(SGLT-2inhibitor+insulin)compared with the placebo group(placebo+insulin)[WMD=0.38,95%CI(0.32,0.45),P<0.00001,I~2=64%].The SGLT-2 inhibitor group lost 2.81 kg[95%CI(2.45,3.17),P<0.00001,I~2=74%,]more than the placebo group.Systolic blood pressure was reduced by 3.17 mmHg[95%CI(2.52,3.83),P<0.00001,I~2=0%]in the SGLT-2 inhibitor group compared with placebo,.The diastolic blood pressure was reduced by 1.37 mmHg[95%CI(0.93,1.81),P<0.00001,I~2=1%,]in the SGLT-2 inhibitor group compared with the placebo group.Reduced fasting blood glucose before breakfast,fasting blood glucose 17.61 mg/dL,[95%CI(12.92,22.31),P<0.00001,I~2=12%,].The incidence of ketoacidosis was higher in the SGLT-2 inhibitor group than in the placebo group.RR=0.29[95%CI(0.19,0.43),P<0.00001,I~2=49.5%],no increase in the risk of hypoglycemia RR=0.98[95%Cl(0.98,1.02),P=0.75,I~2=0%].The incidence of reproductive system infection was higher in the SGLT-2 inhibitor group than in the placebo group.RR=0.33[95%CI(0.21,0.52),P<0.00001,I~2=54%],no increase in the risk of urinary tract infection RR=0.98[95%CI(0.80,1.22),P=0.88,I~2=0%].Conclusion:SGLT-2 inhibitors may become an adjuvant drug to the patients of the type 1 diabetes,but a larger,more sample,multi-center and large-scale clinical trial is needed for safety.In view of the significantly increased risk of ketoacidosis,a further risk-benefit analysis is needed.