Effects of metformin use on aneurysmal subarachnoid hemorrhage outcomes

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.

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.

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]).

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.