| Objective:Currently,sodium-glucose cotransporter 2(SGLT2)inhibitors,a member of insulin-independent classes,are primarily approved for the treatment of patients with type 2 diabetes mellitus(T2DM)as a new oral antihyperglycemic medication.However,in many clinical studies,whether SGLT2 inhibitors in combination with insulin can be used in the treatment of type 1 diabetes mellitus(T1DM)is still controversial.Our objective was to review the available evidence on the efficacy and safety of SGLT2 inhibitor in combination with insulin in the treatment of T1DM,in order to provide more options for the treatment of T1DM.Methods:Randomized clinical trials(RCTs)designed to assess the efficacy and safety of SGLT2 inhibitors for T1DM,were searched on Pubmed,Embase,the Cochrane Library,Clinical Trials.gov,Chinese National Knowledge Infrastructure(CNKI)and Wanfang databases according to the PICOS principle to formulate the retrieval strategy till January 2020.After retrieved clinical RCTs that met inclusion and exclusion criteria,extracted data as well as evaluated quality,statistical meta-analysis were performed using Stata15.Weighted mean difference(WMD)or standardized mean difference(SMD)and 95%confidence interval(CI)were calculated for continuous outcomes.Pooled risk ratio(RR)and 95%CI were calculated for dichotomous outcomes.Results:A total of 15 essays were included,of which 1 for canagliflozin,3 for dapagliflozin,4 for empagliflozin,1 for ipragliflozin,and 6 for sotagliflozin.Sixteen RCTs with 7281 participants were investigated.At the end of the treatment,compared with placebo,SGLT2 inhibitors significantly reduced glycosylated hemoglobin(Hb A1c)by 0.35%[95%CI(-0.38,-0.31)],fasting plasma glucose(FPG)by1.05mmol/L[95%CI(-1.22,-0.88)],mean amplitude of glucose excursion(MAGE)by 0.86mmol/L[95%CI(-1.11,-0.61)],and mean daily glucose(MDG)by 0.93mmol/L[95%CI(-1.06,-0.81)],total daily insulin dose(TDD)by 5.58IU/d[95%CI(-6.82,-4.34)],total bolus daily insulin dose by 2.48IU/d[95%CI(-3.33,-1.62)]as well as total basal daily insulin dose by 3.15IU/d[95%CI(-3.85,-2.45)],but no increased relative risk of hypoglycaemia[RR=1.00,95%CI(0.99,1.01)]or severe hypoglycaemia[RR=0.87,95%CI(0.73,1.03)].In addition,compared with placebo,SGLT2 inhibitors decreased body weight by 2.73kg[95%CI(-3.04,-2.42)],systolic blood pressure by 3.30mm Hg[95%CI(-3.82,-3.79)],diastolic blood pressure by 1.32mm Hg[95%CI(-1.67,-0.97)]and a slight reduction in estimated glomerular filtration rate[WMD=0.96m L/min/1.73m~2,95%CI(-0.37,-0.31)].There was no significant difference in the rate of overall adverse events[RR=1.03,95%CI(0.99,1.08)]、urinary tract infection[RR=1.04,95%CI(0.89,1.22)]、all-cause mortality[RR=0.49,95%CI(0.18,1.30)]or bone fracture[RR=0.87,95%CI(0.63,1.18)],however,SGLT2inhibitors increased the risk of genital infection[RR=3.52,95%CI(2.91,4.26)]and diabetic ketoacidosis(DKA)[RR=4.10,95%CI(2.87,5.84)].Moreover,the low dose empagliflozin(2.5 mg)and sotagliflozin(75 mg)increase the risk of bone fracture,however,the low dose empagliflozin(2.5 mg)did not increase the risk of DKA.Conclusions:Compared with placebo,SGLT2 inhibitors in combination with insulin achieved better glycemic control,greater weight reduction and decreased insulin dose without increasing the risk of hypoglycemia,urinary tract infection,the rate of overall adverse events,or bone fracture,suggesting their potential therapeutic role in T1DM patients.Further more studies were needed to classify the safe appropriate dose to avoid the possible increasing risk of genital infection and DKA. |
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