Neuroprotective Effects of Metformin in Stroke Patients: A Systematic Review and Meta-analysis of Cohort Studies

Clin Neuropharmacol. 2025 Mar-Apr;48(2):51-59. doi: 10.1097/WNF.0000000000000625.

Abstract

Objectives: People with diabetes are 1.5 times more likely to experience stroke than those without diabetes, underlining the urgent need to address this issue. Metformin is often the initial medication chosen to manage diabetes mellitus (DM). The purpose of our systematic review and meta-analysis is to explore the potential neuroprotective effects of metformin in individuals who have received it prior to stroke.

Method: Our study encompassed cohort studies that drew a comparison between the severity and diverse outcomes of stroke among individuals with DM who were administered metformin prior to the stroke event and those with DM who did not receive the treatment.

Results: Ten studies met the eligibility criteria. Prestroke metformin use was associated with a significantly lower National Institutes of Health Stroke Scale score (mean difference = -1.29, 95% confidence interval: -2.11 to -0.47) in ischemic stroke. Metformin pretreatment in ischemic stroke was associated with increased odds of favorable outcome (mRS < 2) at 90 days (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.06 to 1.99), but it was not significant at discharge. Metformin was found to be associated with reduced mortality (OR = 0.52, 95% CI: 0.42 to 0.64) in ischemic stroke. In hemorrhagic stroke, the results showed a significantly lower intracranial hemorrhage volume in prestroke metformin use (mean difference = -4.77, 95% CI: -6.56 to -2.98).

Conclusions: We found that prestroke metformin use in diabetic patients yielded neuroprotective effects. In ischemic strokes, metformin reduces stroke severity and 90-day mortality; it also improves 90-day functional outcomes. In hemorrhagic strokes, prestroke metformin use can also cause less intracranial hemorrhage volume. Further clinical trials are needed to confirm its efficacy and verify its benefits in stroke management.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Cohort Studies
  • Diabetes Mellitus / drug therapy
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Metformin* / pharmacology
  • Metformin* / therapeutic use
  • Neuroprotective Agents* / therapeutic use
  • Stroke* / drug therapy
  • Stroke* / prevention & control

Substances

  • Metformin
  • Neuroprotective Agents
  • Hypoglycemic Agents