Cited by 211Diabetes Treatment and ManagementMetabolism, Diabetes, and CancerCardiovascular Function and Risk Factors

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Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data

Nesti, L., Natali, A.·2017·Nutrition Metabolism and Cardiovascular Diseases

DOI 10.1016/j.numecd.2017.04.009

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Abstract

Background Metformin, the eldest and most widely used glucose lowering drug, is likely to be effective also on cardiac and vascular disease prevention. Nonetheless, uncertainty still exists with regard to its effects on the cardiovascular system as a whole and specifically on the myocardium, both at the organ and cellular levels.Methods We reviewed the available data on the cardiac and vascular effects of metformin, encompassing both in vitro, either tissue or isolated organ, and in vivo studies in experimental animals and humans, as well as the evidence generated by major clinical trials.Results At the cellular level metformin's produces both AMP-activated kinase (AMPK) dependent and independent effects. At the systemic level, possibly also through other pathways, this drug improves endothelial function, protects from oxidative stress and inflammation, and from the negative effects of angiotensin II. On the myocardium it attenuates ischemia-reperfusion injury and prevents adverse remodeling induced by humoral and hemodynamic factors. The effects on myocardial cell metabolism and contractile function being not evident at rest or in more advanced stages of cardiac dysfunction, could be relevant during transient ischemia, during an acute increase in workload and in the early stages of diabetic/hypertensive cardiomyopathy as confirmed by few small clinical trials and some observational studies. The overall evidence emerging from both clinical trials and real world registry is in favor of a protective effect of metformin with respect to both coronary events and progression to heart failure.Conclusions Given this potential, its efficacy and its safety (and also its low cost) metformin remains the central pillar of the therapy of diabetes.

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Authors: Nesti, L., & Natali, A.
Affiliations: University of Pisa (IT)
Corresponding author: Natali, A.
ORCID: Nesti, L.
Natali, A.
Venue: Nutrition Metabolism and Cardiovascular Diseases
Publisher: Elsevier BV
Published: 2017-08
Volume: 27
Issue: 8
Pages: 657-669
ISSN: 0939-4753 (ISSN-L)
DOI: 10.1016/j.numecd.2017.04.009
OpenAlex: W2612188869
Cited by: 211
References: 151
Citations by year: 2026: 4 · 2025: 12 · 2024: 15 · 2023: 21 · 2022: 32 · 2021: 35 · 2020: 32 · 2019: 31 · 2018: 25 · 2017: 4
FWCI: 3.67
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Nutrition Metabolism and Cardiovascular Diseases (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords: metformin, cardiovascular effects, myocardium, AMPK, endothelial function, oxidative stress, inflammation, angiotensin II, ischemia-reperfusion injury, cardiac remodeling, diabetic cardiomyopathy, hypertensive cardiomyopathy, heart failure, coronary events, diabetes treatment
MeSH terms: Animals, Anti-Inflammatory Agents, Antioxidants, Cardiovascular Diseases, Diabetes Mellitus, Endothelium, Vascular, Energy Metabolism, Fibrosis, Heart, Humans, Hypoglycemic Agents, Metformin, Myocardium, Disease Progression, Ventricular Remodeling

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Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data

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