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Long-term effects of metformin on endothelial function in type 2 diabetes: a randomized controlled trial

J de Jager1, A Kooy, C Schalkwijk

  • 1Bethesda Diabetes Research Center, Hoogeveen, The Netherlands; Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands.

Journal of Internal Medicine
|August 29, 2013
PubMed

Insights

Metformin improved endothelial function markers, including von Willebrand factor (vWF) and soluble vascular adhesion molecule-1 (sVCAM-1), in patients with type 2 diabetes. These improvements may explain metformin

Area of Science:

  • Endocrinology
  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Type 2 diabetes is associated with increased risk of atherothrombotic disease.
  • Endothelial dysfunction and inflammation play key roles in atherothrombosis.
  • Metformin is a common medication for type 2 diabetes with potential pleiotropic effects.

Purpose of the Study:

  • To investigate the effect of metformin on endothelial function and inflammatory markers.
  • To determine if these improvements mediate a reduction in atherothrombotic disease risk.

Main Methods:

  • A 4.3-year randomized, placebo-controlled trial involving 390 patients with type 2 diabetes on insulin therapy.
  • Patients received either metformin (850 mg) or placebo, added to their insulin regimen.
  • Measurements included urinary albumin excretion and plasma levels of vWF, sVCAM-1, sE-selectin, t-PA, PAI-1, CRP, and sICAM-1.

Main Results:

  • Metformin significantly reduced levels of vWF, sVCAM-1, t-PA, PAI-1, CRP, and sICAM-1.
  • These reductions, except for CRP, remained significant after adjusting for baseline covariates.
  • Improvements in vWF and sVCAM-1 statistically explained approximately 34% of the observed reduction in cardiovascular morbidity and mortality.

Conclusions:

  • Metformin improves specific markers of endothelial function (vWF, sVCAM-1) in type 2 diabetes patients.
  • These improvements in endothelial function may contribute to the reduced risk of cardiovascular disease associated with metformin therapy.
Abstract

Keywords:
HOME trialcardiovascular disease outcomeendothelial functionmetformintype 2 diabetes

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