In rat models of CKD, metformin demonstrated to ameliorate renal function through its anti-inflammatory and antifibrotic effects mediated by the suppression of the expression of cytokines such as tumor necrosis factor (TNF)-α and β, interleukin (IL)-1β, activation of the adenosine monophosphate-activated protein kinase (AMPK), and decreased phosphorylation of extracellular-signal-regulated kinase 1/2 (ERK1/2) [44,45]. Here, TNF is linked to chronic kidney disease.