Independent-glucose effects of metformin on endothelial dysfunction are not precisely identified, but one study indicates that metformin's therapeutic effects may be related to enhanced eNOS coupling, improved bioavailable NO, (NO/cytotoxic peroxynitrite [ONOO−]) balance, lowered oxidase activity, and other mechanisms beyond glucose regulation that affect endothelial function [64]. The gene discussed is NOS3; the disease is endothelial dysfunction.