Metformin

An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium

Research output: Contribution to journalReview article

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)401-415
Number of pages15
JournalMedical Principles and Practice
Volume24
Issue number5
DOIs
Publication statusPublished - 25 Jul 2015

Fingerprint

Metformin
Endothelium
Pharmaceutical Preparations
AMP-Activated Protein Kinases
Therapeutics
Adenosine Monophosphate
Hypoglycemic Agents
Vascular Diseases
Protein Kinases
Type 2 Diabetes Mellitus
Blood Vessels
Ovary
Respiration
Pharmacokinetics
Insulin

Keywords

  • Cardiovascular disease
  • Diabetes
  • Endothelium
  • Metformin
  • Oxidative stress

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Metformin : An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium. / Kinaan, Mustafa; Ding, Hong; Triggle, Christopher.

In: Medical Principles and Practice, Vol. 24, No. 5, 25.07.2015, p. 401-415.

Research output: Contribution to journalReview article

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