However, it is difficult to rule out possible benefits of metformin on the risk of preeclampsia considering that metformin has been shown to improve endothelial dysfunction, poor vascularization, hypertension, and preeclampsia-related vasoconstriction by reducing soluble fms-like tyrosine kinase-1 and soluble endoglin levels; in addition, modulation of sirtuin 1 activity improves nitric oxide bioavailability through deacetylation of nitric oxide synthase. This evidence concerns the gene FLT1 and preeclampsia.