This drawback of DPP-4 use was in part explained relying on the mechanism of action of these drugs, as they increase insulin secretion and suppresses glucagon secretion, resulting in pathological alterations within the pancreatic tissue and increasing risk of pancreatitis and pancreatic cancer as well (Matveyenko et al., 2009; Andersen et al., 2013), taking into account that these findings were detected after chronic use of DPP-4 inhibitors. This evidence concerns the gene INS and pancreatitis.