An investigation into the pleiotropic activity of metformin. A glimpse of haemostasis

Eur J Pharmacol. 2020 Apr 5:872:172984. doi: 10.1016/j.ejphar.2020.172984. Epub 2020 Feb 1.

Abstract

The most characteristic features of type 2 diabetes mellitus (T2DM) are hyperglycaemia and insulin resistance, however, patients with T2DM are at higher risk of cardiovascular disease (CVD) and atherosclerosis. Diabetes, frequently related to metabolic and vascular impairments, is also associated with thrombosis, increased blood coagulation and an imbalance between coagulation and fibrinolysis. Metformin is the most often used oral glucose-lowering agent; its beneficial properties include lowering insulin resistance, weight reduction and cardioprotection. Available data suggest that the advantageous properties of metformin stem from its favourable effects on endothelium, and anti-oxidative and anti-inflammatory properties. This paper reviews the favourable impact of metformin on endothelial function, with particular emphasis on the release of endogenous molecules modulating the state of the vascular endothelium and coagulation. It also summarizes the present knowledge on the influence of metformin on platelet activity and plasma haemostasis, including clot formation, stabilization and fibrinolysis. Its findings confirm that metformin should constitute first line therapy of T2DM subjects; however, more comprehensive methodical studies are required to discover the full potential of this drug.

Keywords: Biguanides; Coagulation; Diabetes; Endothelium; Haemostasis; Metformin.

Publication types

  • Review

MeSH terms

  • Blood Platelets / drug effects
  • Blood Platelets / physiology
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / pathology
  • Hemostasis / drug effects*
  • Hemostasis / physiology
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Oxidative Stress / drug effects

Substances

  • Hypoglycemic Agents
  • Metformin