Effect of Metformin on Clinical Course of Non-Diabetic Patients with Ischemic Stroke

Abstract

Background: Metformin is commonly used in diabetic patients, but its neuroprotective effects in non-diabetic stroke patients are less understood. This study aimed to evaluate the effect of metformin on the clinical course of acute ischemic stroke in non-diabetic patients. Materials and Methods: In this double-blind randomized clinical trial, 70 non-diabetic patients with acute ischemic stroke confirmed by brain imaging (CT or MRI) within 24 hours of symptom onset were randomly assigned to receive either metformin (500 mg once daily) or placebo for three months, alongside standard care. NIHSS sub-scores were categorized into clinically relevant groups (0=no deficit, 1=mild, 2=moderate, 3=severe) to account for heterogeneity of stroke manifestations. Clinical outcomes, including motor, sensory, visual, and facial function, were assessed at baseline, one, two, and three months. Adverse events were monitored throughout the study. Results: No serious adverse events were observed; mild gastrointestinal symptoms occurred in 2 patients (5.7%) in the metformin group. Compared with placebo, metformin significantly improved overall NIHSS scores at two and three months (P=0.021 and P=0.003), with notable improvements in motor, sensory, facial, and visual functions. Best Gaze remained normal in most patients. These findings are consistent with previous RCTs reporting neuroprotective effects of metformin in non-diabetic stroke patients. Conclusion: Metformin at 500 mg daily for three months is well tolerated and significantly improves neurological outcomes in non-diabetic patients with acute ischemic stroke, particularly in motor, sensory, facial, and visual domains. These results support the potential use of metformin as an adjunct therapy in stroke rehabilitation.