Pathogenetic basis of treating endothelial dysfunction with metformin in patients with diabetes (literature review and own data)

Author:

Sokolova A.M.ORCID,Pushkarev V.V.ORCID,Sokolova L.K.ORCID,Pushkarev V.M.ORCID,Tronko M.D.ORCID

Abstract

Cardiovascular disorders are one of the leading causes of mortality and morbidity worldwide, and their likelihood increases with the addition of risk factors such as sedentary lifestyle, diabetes, obesity, hyperlipidemia, and hypertension. Elevated blood sugar levels can lead to oxidative stress, dyslipidemia, and endothelial dysfunction, culminating in increased cardiovascular risk. Hyperglycemia adversely affects the cardiovascular system, it is a cause of micro- and macrovascular diseases. Harmful biochemical mechanisms of hyperglycemia are associated with the phenomenon of insulin resistance. Metformin (MF) reduces insulin resistance and, therefore, exerts an antihyperglycemic and insulin-lowering effect in patients with type 2 diabetes. MF, like hypolipidemic statins, also has an additional beneficial pleiotropic, anti-inflammatory and antioxidant effect on the vascular system, in addition to its hypolipidemic and antihyperglycemic effects. Primary is the effect of MF on endothelial dysfunction, as endothelial integrity is a critical long-term determinant of vascular health and, therefore, the occurrence of cardiovascular disease. MF has a very simple chemical structure. The simple structure means that the development of new agents with similar or better properties and mechanisms of action is unlikely, so future use of pharmacokinetic, pharmacodynamic and therapeutic targeting data should be expected to unlock the full therapeutic potential of MF. This approach has recently been demonstrated using a sustained-release MF drug that acts in the distal intestine and exhibits intestinal hormone-dependent antihyperglycemic effect. There are virtually no hidden adverse effects for MF, so it has the potential to provide an effective and safe treatment for hyperglycemia in the future, particularly through its beneficial effects on cardiovascular diseases, including endothelial dysfunction and atherosclerosis.

Publisher

Publishing House Zaslavsky

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