Supplementary Material for: Effect of SGLT2 Inhibitors on Risk of Stroke in Diabetes: A Meta-Analysis

<b><i>Background:</i></b> The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on reducing the risk of stroke in patients with type 2 diabetes mellitus (T2DM) remains unclear. Thus, we conducted this systemic review and meta-analysis of all relevant studies and trials to explore the role of SGLT2 inhibitors on the stroke prevention. <b><i>Methods:</i></b> The present study included articles published before October 2021 and searched in Web of Science, PubMed databases. We used STATA 12.0 software to compute hazard ratio (HR) and 95% confidence interval (CI). <b><i>Results:</i></b> Meta-analysis indicated that SGLT2 inhibitors showed no significant effects on risk of stroke in diabetes in randomized controlled trials with a fixed effects model (HR = 0.98; 95% CI: 0.88–1.09, <i>I</i>² = 22.3%, <i>p</i> = 0.272). Compared to other glucose-lowering drugs (oGLD) and insulin, SGLT2 inhibitors alone significantly affected risk of stroke in diabetes in observational studies with a random effects model (HR = 0.87; 95% CI: 0.80–0.95, <i>I</i>² = 72.2%, <i>p</i> &lt; 0.001). <b><i>Conclusions:</i></b> In summary, this meta-analysis indicated that the use of SGLT2 inhibitors did not decrease the risk of stroke. And for some T2DM patients with high-risk factor of stroke, SGLT2 inhibitors therapy may be more suitable compared to some oGLD such as dipeptidyl peptidase-4 inhibitors. The results of this meta-analysis are necessary to be confirmed with further studies and clinical trials.

<b><i>背景：</i></b> 钠-葡萄糖协同转运蛋白2（sodium-glucose cotransporter 2, SGLT2）抑制剂对降低2型糖尿病（type 2 diabetes mellitus, T2DM）患者卒中风险的作用目前仍不明确。为此，本研究针对所有相关研究与试验开展系统评价与荟萃分析，以探讨SGLT2抑制剂在卒中预防中的作用。<b><i>方法：</i></b> 本研究纳入了2021年10月之前发表、检索自Web of Science与PubMed数据库的文献。我们采用STATA 12.0软件计算风险比（hazard ratio, HR）与95%置信区间（confidence interval, CI）。<b><i>结果：</i></b> 荟萃分析结果显示，采用固定效应模型的随机对照试验中，SGLT2抑制剂对糖尿病患者的卒中风险无显著影响（HR = 0.98; 95% CI: 0.88–1.09, <i>I</i>² = 22.3%, <i>p</i> = 0.272）。与其他降糖药物（other glucose-lowering drugs, oGLD）及胰岛素相比，采用随机效应模型的观察性研究显示，单独使用SGLT2抑制剂可显著降低糖尿病患者的卒中风险（HR = 0.87; 95% CI: 0.80–0.95, <i>I</i>² = 72.2%, <i>p</i> < 0.001）。<b><i>结论：</i></b> 综上，本荟萃分析表明，SGLT2抑制剂的使用并未降低卒中风险。而相较于部分其他降糖药物（如二肽基肽酶-4抑制剂），SGLT2抑制剂治疗或许更适用于部分存在卒中高危因素的2型糖尿病患者。本荟萃分析的结果尚需通过进一步研究与临床试验加以验证。