Abstract Body (Do not enter title and authors here): Introduction
Reperfusion injury, defined as the injury to tissue upon restoring blood flow after a period of ischemia, remains a concern in many clinical scenarios such as myocardial infarction and coronary artery bypass surgery. Among several mechanisms of action, metformin, a commonly used antidiabetic medication, has received attention recently for its potential protective effects against reperfusion injury.

Hypothesis
Metformin ameliorates reperfusion injury due to a reduction in myocardial injury markers and improvement in endothelial function across diverse clinical settings.

Methods
A systematic literature search of PubMed, Embase, and Cochrane Library databases up to January 2022 was performed. Metformin's effects on reperfusion injury were identified by searching myocardial injury and endothelial dysfunction. The study included eight articles on metformin and reperfusion injury. Animal studies, expert opinions, and reviews were excluded.

Results
Treatment with metformin significantly lowered myocardial injury markers, with reduced troponin levels: pooled SMD -0.61, 95% CI -0.87 to -0.36, and infarct size by a pooled mean difference of -5.25%, 95% CI -8.96 to -1.53. Additionally, metformin had beneficial effects on the endpoints of endothelial function, including flow-mediated dilation (pooled SMD 0.68, 95% CI 0.38 to 0.97) and markers of oxidative stress and inflammation. Subgroup analysis showed a consistent effect of metformin across different patient populations and different clinical settings. The sensitivity analysis did not indicate the presence of a single study that affected the stability of the result.

Conclusion
This meta-analysis supports the protective effect of metformin against reperfusion injury in various clinical settings. Metformin appears to reduce myocardial injury and promote improvement in endothelial function, which may translate into reducing the risk of adverse cardiovascular events among patient populations at high risk for them. Further research is warranted to investigate the mechanisms for its cardioprotective effect.