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| |  Positive Long-Term Effects of Metformin on Endothelial Function and Inflammation in People With Type 2 Diabetes Treated With Insulin: Presented at IDF By Brian Hoyle MONTREAL -- October 21, 2009 -- Treatment with metformin improves the function of endothelial cells and reduces low-grade inflammation, according to a multi-institutional study from the Netherlands presented here at the 20th World Diabetes Congress of the International Diabetes Federation (IDF). Adriaan Kooy, MD, PhD, Bethesda Diabetes Research Center and Bethesda General Hospital, Hoogeveen, the Netherlands, presented the results from the first long-term randomised study of the effects of metformin in people with type 2 diabetes on October 20. According to the American Heart Association, among those with diabetes, cardiovascular diseases are the leading cause of morbidity and mortality, with diabetic adults being at 2 to 4-fold higher risk of cardiovascular disease than nondiabetics.(1) The reduced rates of cardiovascular disease and death associated with metformin treatment have been suggested to be a consequence of boosted endothelial function and reduced inflammation. This study examined the effects of metformin on several markers of endothelial function (urinary albumin excretion, von Willebrand factor [vWf], soluble vascular cell adhesion molecule-1 [sVCAM-1], sE selection, tissue plasminogen activator [tPA], and plasminogen activator inhibitor-1 [PAI-1]) and markers of low-grade inflammation (plasma C-reactive protein [CRP] and soluble intercellular adhesion molecule-1 [sICAM-1]) in patients with type 2 diabetes who randomly received metformin (n = 196) or placebo (n = 194). The completion rate was 72% (n = 277). At the 4.3-year follow-up, plasma samples were obtained, and the levels of the various markers were ascertained. The means of each marker were added together to calculate overall scores (z scores) for endothelial function and inflammation. Compared with placebo, metformin use significantly (P < .001) decreased vWf (11%), sVCAM-1 (5%), tPA (15%), PAI-1 (21%), and the endothelial z score (7%). Metformin also produced significant decreases in CRP (17%; P = .036), sICAM-1 (-5%; P = .004), and the inflammation z score (-5%; P = .074). “Except for sVCAM-1, the metformin reductions were independent of metformin-associated changes in Hb A1C, insulin dose, and weight. The reduction in sVCAM-1 was entirely mediated through metformin improved glycaemic control and reduced insulin levels,” said Dr. Kooy. The researchers concluded that metformin treatment is associated with a decrease in plasma concentrations of markers for endothelial function and inflammation, reflecting an improvement of endothelial regulation of haemostasis, leukocyte adhesion, and fibrinolysis and a reduction in low-grade inflammation. “Metformin may have specific effects on endothelial function, which may explain, in part, why it is associated with a decreased risk of cardiovascular disease in type 2 diabetes,” said Dr. Kooy. Funding for this study was provided by Altana, E. Merck Serono, Lifescan, Novo Nordisk, Eli Lilly, Novartis, and Merck, Sharp, & Dohme. 1. Eckel RH et al. Circulation 2006;113:2943-2946.
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