DPP 4 Inhibitors Mechanism Of Action

DPP4 is a serine protease that is widely distributed throughout the body, expressed as an ectoenzyme on endothelial cells, on the surface of Tlymphocytes, and in a circulating form. DPP4 cleaves the two Nterminal amino acids from peptides with a proline or alanine in the second position. Although there are many potential substrates for this enzyme, it seems to be especially critical for the inactivation of GLP1 and GIP glucosedependent insulinotropic polypeptide; gastric inhibitory peptide. DPP4 inhibitors increase the AUC of GLP1 and GIP when their secretion is by a meal. Several agents provide nearly complete and longlasting inhibition of DPP4, thereby increasing the proportion of active GLP1 from 1020 of total circulating GLP1 immunoreactivity to nearly 100. Two of these, sitagliptin and saxagliptin are now available in the U. S.; a third, vildagliptin, is available in the E. U.; a fourth compound, alogliptin, is in advanced stages of clinical trials. Sitagliptin and alogliptin