BACKGROUND: Metformin is a commonly prescribed oral hypoglycemic agent for diabetic patients. Its effect in reducing the incidence of stroke has already been proven. We aimed to explore the impact of prior metformin use on stroke outcomes. METHODS: The Web of Science, PubMed, Embase, and Cochrane Library were searched to identify relevant studies involving stroke patients with a history of metformin use and comparing them to non-metformin users. We analyzed the following outcomes: modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), mortality, or length of hospitalization. RESULTS: Eleven studies, with 13,825 participants, were included. The metformin group showed higher favorable mRS 0 - 2 than the non-metformin group (risk ratio (RR) = 1.14, 95% confidence interval (CI): 1.09 - 1.19, P value <
0.01). Also, significantly lower mortality rates were seen in the metformin group (RR = 0.54, 95% CI: 0.46 - 0.63, P value ≤ 0.01). NIHSS at discharge was lower in the metformin group than the non-metformin group (mean difference (MD) = -0.46, 95% CI: -0.82 - -0.11, P value <
0.01). The mRS 3 - 6 indicates less favorable outcomes were higher in the non-metformin group (RR = 0.85, 95% CI: 0.77 - 0.93). At the same time, NIHSS at admission showed no statistically significant difference between the two groups. These results indicate that metformin has a beneficial impact on the severity of stroke. CONCLUSIONS: Pre-stroke metformin therapy is associated with better post-stroke clinical outcomes and lower mortality rates. These results highlight the potential neuroprotective role of metformin and emphasize its role as an adjunctive treatment in stroke management. Further research is required to understand its mechanism better.