Confirmation also comes from a larger randomized placebo-controlled study with 390 patients treated with metformin (850 mg/tid) and a 4.3 year follow up that demonstrated that metformin lowered the plasma levels of biomarkers of inflammation and endothelial dysfunction including CRP, C-reactive protein; von Willebrand factor, vWF; soluble vascular adhesion molecule-1, sVCAM-1; soluble E-selectin, sE-selectin; tissue type plasminogen activator, t-PA; and plasminogen activator inhibitor-1, PAI-1 [31]. Here, CRP is linked to endothelial dysfunction.