Metformin Improves Endothelial Function in Type 2 Diabetes: Presented at EASD
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Metformin Improves Endothelial Function in Type 2 Diabetes: Presented at EASD

By Bruce Sylvester

VIENNA, Austria -- October 7, 2009 -- Metformin appears to have specific effects on endothelial function, which might help explain why metformin treatment is associated with decreased risk of cardiovascular disease in type 2 diabetes, researchers reported here October 2 at the 45th Annual Meeting of the European Association for the Study of Diabetes (EASD).

Adriann Kooy, MD, Bethesda Diabetes Research Center Hoogeveen, and the University Medical Center. Maastricht, the Netherlands, and colleagues enrolled 390 patients with type 2 diabetes being treated with insulin.

Patients were randomised to receive either metformin (n = 196) or placebo (n = 194) plus insulin for 4.3 years. The investigators aimed for similar levels of glycaemic control between the groups.

At baseline and at months 4, 17, 30, 43 and 52, plasma samples were taken to measure markers of endothelial function. These included urinary albumin excretion and plasma levels of von Willebrand factor (vWf), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E (sE)-selectin, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), C-reactive protein (CRP), and soluble intercellular adhesion molecule-1 (sICAM-1).

Metformin treatment versus placebo was associated with a decrease in vWf of 11% (P < .001); a decrease in sVCAM-1 of 5% (P < .001); a decrease in t-PA of 15% (P < .001); a decrease in PAI-1 of 21% (P = .001); and a decrease in the endothelial dysfunction standard deviation score of 7% (P < .001).

Changes in urinary albumin excretion and sE-selectin were not significant.

Metformin treatment versus placebo was associated with a decrease in CRP of 17% (P = .036); a decrease in sICAM-1 of -5% (P = .004); and a decrease in the inflammation standard deviation score of -5% (P = .074).

“Improvements in endothelial function explained about 35% of the reduced risk of macrovascular morbidity and mortality associated with the use of metformin,” said Dr. Kooy.

[Presentation title: Long-Term Effects of Metformin on Endothelial Function and Inflammation in Type 2 Diabetes Treated With Insulin: A Randomized, Placebo-Controlled Trial. Abstract 861]

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