| Background and ObjectiveThe mortality and social-economic burden caused by diabetes and its complications are increasing continuously.Diabetes are associated with several cardiovascular diseases,like cancer,infection,osteoprosis etc.But cardiovascular events are most common cause of death.Thus,individualized treatment is required for diabetic patients.For patients with diabetes complicated with cardiovascular disease,besides controlling glucose,it’s also important that we should pay attention to the influence of hypoglycemic drugs on the cardiac and renal outcomes of diabetic patients.Many clinical studies have confirmed that SGLT2 inhibitor can reduce cardiovascular risk and major cardiovascular events of diabetic patients,but its impact on stroke is still unclear.In this study,the effects of SGLT2 inhibitors on stroke and adverse events related with cardiovascular and drug were systematically evaluated and meta-analyzed.MethodsSearch Pubmed,Embase,Cochrane,Web of science databases by Mesh Term and Text Word system.The search words are"Type2 diabetes","sglt2 inhibitors","stroke",etc.The search time is until January 31th,2021.Clinical,randomized,placebo-controlled study including the effect of SGLT2 inhibitor intervention on stroke in patients with type 2 diabetes mellitus was included.The main outcomes were the effects of SGLT2 inhibitors on stroke and non-fatal stroke,and the secondary outcomes were the effects of SGLT2 inhibitors on adverse events（death from any cause,death from cardiovascular causes,diabetic ketoacidosis,urinary tract infection,acute renal injury,fractures,lower limb amputation）.For the research results,the odds ratio（OR）is used as the effect quantity,and the 95%confidence interval（CI）is expressed.The heterogeneity of the study was evaluated by I~2test statistics and Chi-square test（X~2）,and further sensitivity analysis was carried out when the heterogeneity of the statistical results was high.Whatever the heterogeneity was,the random effect model was used for analysis.P≤0.05,which means it is statistically significant.ResultThere are 9 studies were included eventually,all of which were randomized controlled trials published in English.A total of 49855 patients with type 2 diabetes were enrolled in the study,with a trial cycle ranging from 24 weeks to 219 weeks.The results of Meta analysis showed that there was no significant influence of stroke in SGLT2 inhibitor versus placebo[P=0.85,M-H OR=0.99,95%CI（0.89,1.10）,I~2=0%],and there was no significant difference in the incidence of non-fatal stroke between placebo and placebo[P=1.00,M-H OR=1.00 95%CI（0.86,1.16）,I~2=7%].The rate of death from any cause of SGLT2 inhibitors was prior to placebo group[P=0.0003,M-H OR=0.88 95%CI（0.82,0.94）,I~2=0%];the incidence of death from cardiovascular events of SGLT2 inhibitors was improved compared with placebo group[P=0.01,M-H OR=0.84 95%CI（0.73,0.96）,I~2=50%].In drug-related adverse events,SGLT2inhibitors significantly increased the risk of DKA compared with the placebo group[P=0.004,M-H OR=2.53,95%CI（1.34,4.76）,I~2=23%],and the risk of UTI was significantly higher than that of the placebo group[P=0.02,M-H OR=1.16,95%CI（1.03,1.31）,I~2=19%].The AKI in the placebo group was significantly better than that in the placebo group[P=0.0001,M-H OR=0.76,95%CI（0.66,0.87）I~2=0%].The incidence of fracture was higher than that in the placebo group,but there was no significant difference between the two groups.The incidence of fractures in the placebo group was significantly higher than that in the placebo group,but there was no significant difference between the two groups[P=0.16,M-H OR=1.14,95%CI（0.95,1.38）,I~2=66%].The risk of lower limb amputation was slightly higher in the placebo group than in the placebo group,but there was no significant difference between the two groups[P=0.26,M-H OR=1.11,95%CI（0.93,1.32）,I~2=0%].Limitations:The studies included in our meta-analysis are all sub-studies of SGLT2 inhibitors on cardiovascular studies in patients with diabetes,and there is a lack of clinical randomized controlled trials of SGLT2 inhibitors alone on stroke,so there may be bias in our study.In addition,the number of studies included was limited because this study excluded related studies with a small sample size and non-placebo in the control group.A large sample size and more clinical randomized controlled trials are needed for further research.ConclusionsThe results of meta analysis suggest that SGLT2 inhibitors have no significant effect on stroke and non-fatal stroke,but play a positive role in the improvement of death from any cause and cardiovascular death.In addition,SGLT2 inhibitors significantly increased the risk of diabetic ketoacidosis and urinary tract infection,slightly increased the risk of fracture（especially Canagliflozin）and amputation of lower limbs,but had no significant statistical difference,and significantly decrease the risk of acute kidney injury compared with the placebo.Significance of the main findings:compared with similar studies published a few years ago,this meta analysis included the latest large CVOT of SGLT2 inhibitors,such as CREDENCE,VERTIS,CVSOLOIST-WHF,etc.As well as newly approved FDA drugs such as Ertugliflozin and Sotagliflozin,which provided an evidence-based basis for the latest SGLT2inhibitors on stroke-related effects and adverse events related with cardiovascular and drug. |
PDF Full Text Request