American Journal of Cardiovascular Drugs

, Volume 18, Issue 3, pp 181–193 | Cite as

Cardioprotection by Metformin: Beneficial Effects Beyond Glucose Reduction

  • Leon Varjabedian
  • Mohammad Bourji
  • Leili Pourafkari
  • Nader D. NaderEmail author
Review Article


Metformin is a biguanide that is widely used as an insulin-sparing agent to treat diabetes. When compared with the general population, diabetics are twice as likely to die from fatal myocardial infarction and congestive heart failure (CHF). There has been a significant concern regarding the use of metformin in patients with CHF because of their higher tendency to develop lactic acidosis. However, large epidemiological trials have reported better cardiovascular prognosis with metformin compared to other glucose-lowering agents among diabetics. Additionally, metformin has reduced the risk of reinfarction and all-cause mortality in patients with coronary artery disease and CHF, respectively. The protection against cardiovascular diseases appears to be independent of the anti-hyperglycemic effects of metformin. These effects are mediated through an increase in 5′ adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and by increased phosphorylation of endothelial nitric oxide synthase (eNOS) in cardiomyocytes with an increased production of nitric oxide (NO). Metformin preconditions the heart against ischemia-reperfusion injury and may improve myocardial remodeling after an ischemic insult. The preponderance of evidence currently suggests that metformin is safe in patients with CHF, prompting the Food and Drug Administration to remove CHF as a contraindication from the package insert of all generic metformin preparations. In this narrative, along with a limited meta-analysis of available studies, we have reviewed the pleiotropic (non-glucose-lowering) effects of metformin that potentially contribute to its cardioprotective properties. Additionally, we have reviewed issues surrounding the safety of metformin in patients with cardiac diseases.



No external funding was used in the preparation of this manuscript.

Compliance with Ethical Standards

Conflict of interest

Leon Varjabedian, Mohammad Bourji, Leili Pourafkari and Nader D. Nader declare that they have no conflict of interest that might be relevant to the contents of this manuscript.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Leon Varjabedian
    • 1
  • Mohammad Bourji
    • 2
  • Leili Pourafkari
    • 3
  • Nader D. Nader
    • 3
    Email author
  1. 1.Carilion Roanoke Memorial HospitalRoanokeUSA
  2. 2.Department of MedicineUniversity at BuffaloBuffaloUSA
  3. 3.Department of AnesthesiologyUniversity at BuffaloBuffaloUSA

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