Meta-analysis Of Efficacy And Safety Of SGLT2 Inhibitors In The Treatment Of Type 2 Diabetes Mellitus With Cardiovascular Disease

Objective: Sodium-glucose cotransporter 2(SGLT2)inhibitor is a new type of drug for the treatment of type 2 diabetes mellitus complicated with cardiovascular disease,but its efficacy and safety are still controversial.This study firstly used Meta-analysis to evaluate the efficacy and safety of SGLT2 inhibitors in the treatment of type 2 diabetes complicated with cardiovascular disease,and then used network Meta-analysis to rank the differences in efficacy and safety of SGLT2 inhibitors.The application provides theoretical reference basis.Methods: The effectiveness of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus complicated with cardiovascular disease was searched in CNKI,VIP Journal Resource Database,Wanfang Database,China Biomedical Literature Database,Pub Med,Cochrane Library,Embase,Clinical Trials,Ovid and other databases.Literatures related to safety were screened according to pre-established inclusion and exclusion criteria,and clinical randomized controlled trial(RCT)data were obtained.The search language was limited to Chinese and English.For the included data,Rev Man5.3 software was used for meta-analysis to evaluate the efficacy and safety of SGLT2 inhibitors in the treatment of type 2 diabetes complicated with cardiovascular disease,and then Stata14.0 software was used to conduct network meta-analysis to evaluate SGLT2 inhibitors differences in efficacy and safety among each other.Efficacy outcomes included the incidence of major cardiovascular events(including the composite endpoint of cardiovascular death,myocardial infarction,and stroke),the composite endpoint of cardiovascular death or hospitalization for heart failure,the incidence of cardiovascular death,the incidence of myocardial infarction,The incidence of stroke,hospitalization for heart failure,and all-cause mortality.Safety outcomes included the incidence of serious adverse events,fractures,amputations,diabetic ketoacidosis,hypoglycemia,urinary The incidence of road infection and acute kidney injury.Results: After searching the database,a total of 6882 literatures were obtained,and 12 RCTs(58374 patients in total)met the inclusion criteria,and the quality of the included literatures was high.(1)Effectiveness:1)Meta analysis: Compared with placebo,the incidence of major cardiovascular events in the SGLT2 inhibitor group [OR=0.91,95%CI(0.85,0.97),P=0.006],the composite endpoint of cardiovascular death or hospitalization for heart failure Incidence rate [OR=0.78,95%CI(0.72,0.84),P<0.00001],cardiovascular death rate [OR=0.89,95%CI(0.81,0.96),P=0.005],heart failure hospitalization rate [OR=0.68,95%CI(0.63,0.74),P<0.00001] and the 95%CI for all-cause mortality [OR=0.88,95%CI(0.83,0.95),P=0.0003] did not include 1 And P≤0.05,the efficacy was significantly better than placebo,but SGLT2 inhibitors could not significantly reduce the incidence of myocardial infarction [OR=0.95,95%CI(0.85,1.05),P=0.32] and the incidence of stroke [OR=0.98,95%CI(0.85,1.13),P=0.75].2)Network meta-analysis:(1)Probability ranking of drugs to improve major cardiovascular events:placebo(14.5%)< ertugliflozin(20.6%)< dapagliflozin(46.0%)< empagliflozin(79.4%)< canagliflozin(89.5%)(2)Probabilistic ranking of drugs to improve the composite end point of cardiovascular death or hospitalization for heart failure:placebo(6.0%)< ertugliflozin(31.6%)< dapagliflozin(56.6%)< canagliflozin(76.8%)< empagliflozin(79.0%)(3)Probability ranking of drugs to improve cardiovascular death:placebo(14.4%)< ertugliflozin(46.1%)< empagliflozin(46.3%)< dapagliflozin(61.3%)< canagliflozin(81.9%)(4)Probabilistic ranking of drugs to improve heart failure hospitalization:placebo(0.1%)< dapagliflozin(47.9%)< ertugliflozin(56.9%)< empagliflozin(66.3%)< canagliflozin(78.8%)(5)Probability ranking of drugs to improve all-cause mortality:placebo(11.7%)< ertugliflozin(46.5%)< empagliflozin(47.7%)< canagliflozin(69.5%)< dapagliflozin(74.5%)(2)Safety:1)Meta analysis: Compared with placebo,serious adverse events caused by SGLT2 inhibitors [OR=0.89,95%CI(0.86,0.93),P<0.00001],acute kidney injury [OR=0.74,95%CI(0.65,0.84),P<0.00001],hypoglycemia [OR=0.90,95%CI(0.82,0.98),P=0.46] and other adverse reactions occurred less frequently,the 95%CI did not contain 1,and the forest plot mostly fell within On the side of the drug,the safety is relatively good,with a statistical difference.However,compared with placebo,SGLT2 inhibitors have a higher probability of causing diabetic ketoacidosis [OR=3.32,95%CI(1.99,5.53),P<0.00001],which should be paid more attention in clinical practice.In addition,amputations due to SGLT2 inhibitors [OR=1.12,95%CI(0.95,1.32),P=0.18],fractures [OR=1.22,95%CI(0.97,1.53),P=0.09],urinary tract infections [OR=1.10,95%CI(0.98,1.23),P=0.04] and other adverse reaction rates were similar to placebo,and there was no significant difference in safety,which was not statistically significant.2)Network meta-analysis:(1)Probability ranking of drugs not likely to cause serious adverse events:empagliflozin(97.3%)> dapagliflozin(62.6%)> canagliflozin(42.7%)> ertugliflozin(41.9%)> placebo(5.5%)(2)Probability ranking of drugs not likely to cause Hypoglycemic events:empagliflozin(90.3%)> dapagliflozin(76.4%)> ertugliflozin(43.8%)> canagliflozin(21.6%)> placebo(18.0%)(3)Probability ranking of drugs not likely to cause Acute kidney injury:empagliflozin(79.7%)> dapagliflozin(69.6%)> canagliflozin(55.4%)> ertugliflozin(40.1%)> placebo(5.2%)(4)Probability ranking of drugs not likely to cause Diabetic ketoacidosis:Placebo(95.4%)> dapagliflozin(56.7%)> empagliflozin(38.1%)> canagliflozin(31.7%)> ertugliflozin(28.2%)Conclusion: Compared with placebo,SGLT2 inhibitors have better efficacy in the treatment of type 2 diabetes complicated with cardiovascular disease,and are relatively safe.Canagliflozin(89.5%)was relatively effective in reducing the incidence of major cardiovascular events(including the composite endpoint of cardiovascular death,myocardial infarction,and stroke),and empagliflozin(79.0%)was effective in reducing cardiovascular death.Or the efficacy of the composite endpoint of hospitalization for heart failure was relatively better.However,empagliflozin(97.3%)produced relatively fewer serious adverse events than canagliflozin(42.7%)and was relatively safe.In addition,in the process of drug use,more attention should be paid to the occurrence of diabetic ketoacidosis,and the efficacy and safety of the drug should be considered comprehensively.In terms of clinical application,this study tends to recommend the optimal treatment measure empagliflozin.Conclusions still need more high-quality,large-sample RCTs for validation and supplementation.