Diabetes: Chronic Metformin Treatment and Outcome Following Acute Stroke

AIM: To evaluate if in patients with known diabetes, pretreatment metformin will lead to less severe stroke, better outcome, and lower mortality following acute stroke. METHODS: The Qatar stroke database was interrogated for stroke severity and outcome in patients with ischemic stroke. Outcome was compared in nondiabetic vs. diabetic patients and in diabetic patients on metformin vs. other hypoglycemic agents. The National Institute of Health Stroke Scale was used to measure stroke severity and 90-day modified Rankin scale (mRS) score to determine outcome following acute stroke. RESULTS: In total, 4,897 acute stroke patients [nondiabetic: 2,740 (56%) and diabetic: 2,157 (44%)] were evaluated. There were no significant differences in age, risk factors, stroke severity and type, or thrombolysis between the two groups. At 90 days, mRS (shift analysis) showed significantly poor outcome in diabetic patients (p < 0.001) but no differences in mortality. In the diabetic group, 1,132 patients were on metformin and 1,025 on other hypoglycemic agents. mRS shift analysis showed a significantly better outcome in metformin-treated patients (p < 0.001) and lower mortality (8.1 vs. 4.6% p < 0.001). Multivariate negative binomial analyses showed that the presence of diabetes negatively affected the outcome (90-day mRS) by factor 0.17 (incidence risk ratio, IRR, 1.17; CI [1.08–1.26]; p < 0.001) when all independent variables were held constant. In diabetic patients, pre-stroke treatment with metformin improved the outcome (90-day mRS) by factor 0.14 (IRR 0.86 [CI 0.75–0.97] p = 0.006). CONCLUSION: Similar to previous reports, our study shows that diabetes adversely affects stroke outcome. The use of prior metformin is associated with better outcome in patients with ischemic stroke and results in lower mortality. The positive effects of metformin require further research to better understand its mechanism.