KDR and retinal disorder: Joe et al. (2015) found that metformin possesses an antiangiogenic effect in mouse oxygen-induced retinopathy and is undermodulated by reducing the vascular endothelial growth factor receptor Flk-1. Other research found that metformin can alter and regulate the downregulation of microRNA (miR)-21 by upregulating TGF-β to enhance the antiangiogenic mechanism (Wang et al., 2020).