Effects of Metformin on the Cardiovascular System of Patients with Diabetes, but Also Without It
Diabetes mellitus (DM) is considered an independent risk factor for the development of ischemic heart disease (IHD). The prevalence of IHD is continuously increasing, making early detection of risk factors and their elimination crucial in reducing morbidity and mortality of all at-risk patients. Metformin is still recommended as the first-line drug for patients with type 2 DM by experts. In addition to its effects leading to a reduction in blood glucose levels, it also has a cardioprotective effect. Recently, studies focusing on primary and secondary cardiovascular prevention in patients with and without DM have been concentrating on it.
Systemic Effects
The primary systemic effect of metformin is the reduction of morning fasting blood glucose levels by decreasing glucose production in the liver, slowing down gluconeogenesis, and increasing glucose utilization in muscles. Numerous studies have also shown an increase in glucagon-like peptide 1 (GLP-1) levels during metformin treatment, in patients with and without DM. At the molecular level, metformin inhibits the formation of advanced glycation end-products (AGE), which occur during chronic hyperglycemia by binding glucose to proteins, mostly disrupting their function. Metformin treatment also positively affects systemic inflammation, reduces oxidative stress, and aids in weight reduction. A significant advantage is the synergistic action of metformin with other antidiabetic drugs.
Effects on the Cardiovascular System
Observational studies in recent years have demonstrated that patients with type 2 DM who managed to maintain lower glycated hemoglobin (HbA1c) levels during the first 6 months of treatment achieved better cardiovascular outcomes.
Treatment with metformin positively influences blood vessels – metformin reduces the formation of atherosclerotic plaques, calcifications, and promotes vasodilation in the vascular endothelium. It has mildly positive effects on lipid profiles, mainly reducing LDL cholesterol and triglyceride levels, while its impact on HDL cholesterol is lesser. Some smaller studies suggest that metformin may exhibit similar beneficial effects in certain patients without DM (for example, those with heart failure with preserved ejection fraction) as it does in patients with type 2 DM.
Conclusion
The key to successful type 2 DM treatment is therapy individualization. Type 2 DM is a chronic disease – initially, patients have only a small cardiovascular risk, but it increases as the disease progresses. Metformin has already demonstrated beneficial cardiovascular effects in patients with type 2 DM and it appears that some at-risk cardiac patients without DM could also benefit from it. To determine which specific groups would benefit most from metformin treatment, further detailed studies are necessary.
(epa)
Sources:
1. Luo F., Das A., Chen J. et al. Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management. Cardiovasc Diabetol 2019; 18 (1): 54, doi: 10.1186/s12933-019-0860-y.
2. Zilov A. V., Abdelaziz S. I., AlShammary A. et al. Mechanisms of action of metformin with special reference to cardiovascular protection. Diabetes Metab Res Rev 2019; 35 (7): e3173, doi: 10.1002/dmrr.3173.
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