Comparative Effect of Glucose-Lowering Drugs for Type 2 Diabetes Mellitus on Stroke Prevention: A Systematic Review and Network Meta-Analysis

There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks. Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], -0.17; 95% confidence interval [CI], -0.27 to -0.07). In the network meta- analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively. SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.