Metformin: An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium Review uri icon

Overview

MeSH Major

  • AMP-Activated Protein Kinases
  • Endothelium
  • Metformin
  • Neoplasms
  • Vascular Diseases

abstract

  • The anti-diabetic and oral hypoglycaemic agent metformin, first used clinically in 1958, is today the first choice or 'gold standard' drug for the treatment of type 2 diabetes and polycystic ovary disease. Of particular importance for the treatment of diabetes, metformin affords protection against diabetes-induced vascular disease. In addition, retrospective analyses suggest that treatment with metformin provides therapeutic benefits to patients with several forms of cancer. Despite almost 60 years of clinical use, the precise cellular mode(s) of action of metformin remains controversial. A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK. Discrepancies, however, between the concentrations of metformin used in in vitro studies versus therapeutic levels suggest that caution should be applied before extending inferences derived from cell-based studies to therapeutic benefits seen in patients. Conceivably, the effects, or some of them, may be at least partially independent of AMPK and/or mitochondrial respiration and reflect a direct effect of either metformin or a minor and, as yet, unidentified putative metabolite of metformin on a target protein(s)/signalling cascade. In this review, we critically evaluate the data from studies that have investigated the pharmacokinetic properties and the cellular and clinical basis for the oral hypoglycaemic, insulin-sensitising and vascular protective effects of metformin. © 2015 S. Karger AG, Basel.

publication date

  • January 2015

Research

keywords

  • Review

Identity

Language

  • eng

PubMed Central ID

  • PMC5588255

Digital Object Identifier (DOI)

  • 10.1159/000381643

PubMed ID

  • 26021280

Additional Document Info

start page

  • 401

end page

  • 15

volume

  • 24

number

  • 5