Supplementary Material for: Efficacy and Safety of Glibenclamide on Functional Outcomes and Cerebral Edema Following Ischemic and Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective: This systematic review and meta-analysis aims to evaluate the clinical and radiological outcomes of glibenclamide versus control in acute stroke. Methods: In accordance with PRISMA guidelines, a comprehensive literature search was conducted to identify relevant studies up to January 15, 2025. Efficacy outcomes included modified Rankin Scale (mRS) score at 3 and 6 months, Barthel Index (BI), midline shift (MLS) at 72–96 hours, serum MMP-9 levels and decompressive craniectomy. Safety analysis assessed the incidence of hypoglycemia, mortality, and serious adverse events (SAE). Results: A total of seven randomized controlled trials involving 1,225 patients were included in the meta-analysis. No statistically significant differences were observed in the efficacy outcomes in the pooled analysis. In subgroup analysis of mRS, glibinclamide was superior in intracerebral hemorrhage (MD= -0.67, 95% CI [-1, -0.34], p-value < 0.0001) but not ischemic or subarachnoid hemorrhage subtypes (MD= -0.03, 95% CI [-0.34, 0.28], p-value= 0.86) and (MD= 0.06, 95% CI [-0.6, 0.71], p-value= 0.86) respectively. In terms of safety, there were no significant differences in SAE or mortality (OR= 1.34, 95% CI [0.99, 1.8], p-value= 0.06) and (OR= 0.67, 95% CI [0.31, 1.45], p-value= 0.31) respectively. However, glibenclamide was associated with an increased risk of hypoglycemia (OR= 5.03, 95% CI [2.17, 11.66], p-value= 0.0002). Conclusion: The use of glibenclamide did not demonstrate improved outcomes in patients with acute stroke. However, real-time pharmacokinetic monitoring, identifying optimal administration route, and patient subgroups, that may potentially benefit from glibenclamide are essential before the drug’s efficacy can be conclusively determined.