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 glycemic 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.

EASD: 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