Can metformin use reduce the risk of stroke in diabetic patients? A systematic review and meta-analysis

Stroke and cardiovascular diseases are major causes of death and disability, especially among diabetic patients. Some studies have shown that metformin has been effective in preventing cardiovascular diseases. In this study, we aim to evaluate the effect of metformin on stroke in type 2 diabetic patients.

A comprehensive search was conducted in Medline, Embase, Scopus, and Web of Science databases from their inception till 1st July 2022. Randomized clinical trials (RCT) and cohort studies were included. Two independent researchers screened the records, extracted the data, and assessed the risk of bias and certainty of evidence. Findings were reported as risk ratio (RR) and 95% confidence interval (CI). All statistical analyses were performed using the STATA 17.0 software package.

Analysis of 21 included studies with 1,392,809 patients demonstrated that metformin monotherapy was effective in reducing stroke risk in both RCTs (RR = 0.66, 95% CI: 0.50, 0.87 p = 0.004) and cohort studies (RR = 0.67, 95% CI: 0.55, 0.81, p < 0.0001). However, combined administration of metformin with other antihyperglycemic agents had no significant effect on stroke risk reduction in either the RCTs (RR = 0.92, 95% CI: 0.69, 1.22 p = 0.558) or the cohort studies (RR = 0.79, 95% CI: 0.59, 1.06, p = 0.122).

Low to moderate level of evidence in RCTs showed that metformin monotherapy could reduce stroke risk in type 2 diabetic patients. However, the preventive effect of metformin in stroke was not observed in patients who received a combination of metformin plus other hypoglycemic agents.