Abstract
Background: Metformin is widely prescribed and has neuroprotective effects in animals, but its impact on brain injury after aneurysmal subarachnoid hemorrhage (aSAH) in humans is unclear. Methods: This single-center retrospective review assessed patients with aSAH from 2009 to 2023, categorizing them based on pre-admission metformin use. The primary outcome was delayed cerebral ischemia (DCI), while secondary outcomes included in-hospital mortality, rebleeding, angiographic cerebral vasospasm (CVS), and favorable modified Rankin Scale (mRS) scores at discharge and the 3-month follow-up. Outcomes were analyzed using logistic regression. Sensitivity analysis was performed after excluding patients receiving comfort care. Results: A total of 900 patients were included (47 metformin and 853 non-metformin). DCI rates were similar between groups (38.3% vs. 29.3%, aOR = 1.06 [0.49–2.28]). Rebleeding rates were 4.3% for metformin users and 5.6% for non-users (aOR = 0.47 [0.09–2.51]). In-hospital mortality was 4.3% in metformin users vs. 9.7% in non-users (aOR = 0.47 [0.08–2.84]). Angiographic CVS was 38.3% in metformin users and 52.8% in non-users (aOR = 0.49 [0.23–1.05]), and at 7 days, CVS was 29.8% vs. 47.6% (aOR = 0.46 [0.21–1.01]). Sensitivity analysis showed similar DCI rates (39.1% vs. 30.9%, aOR = 0.98 [0.45–2.15]) but lower CVS at 7 days for metformin users (aOR = 0.44 [0.20–0.98]). Conclusion: Metformin use before aSAH did not significantly affect the risk of DCI or CVS. However, after excluding comfort care patients, the findings are highly speculative of reduced CVS risk at 7 days post-aSAH. Rebleeding and mortality rates were similar across groups. Future research with larger, multi-institutional datasets is needed to better understand metformin's impact, particularly during and after aSAH. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.