Double Edge Effect of Dpp4 Inhibitor Sitagliptin, a Type-2 Anti-Diabetic Drug, on Inflammation, Injury and Cancer

Abstract

Maintaining a healthy glycaemic condition is associated with so many more other protective/precautionary attributes. Recent advancement in the field of drug discovery have led us find more and more options to choose from. DPP-4 inhibitor sitagliptin makes sustained expression of incretins GLP-1 and GIP that in turn establishes glycaemic control. But recent reports claimed pro-inflammatory as well as pro-carcinogenic action of the drug after prolonged use in T2DM patients. Interestingly, in those cases also, the effector molecule responsible is said to be the incretin GLP-1. The same molecule has been hypothesized for being responsible to cause thyroid C-cell carcinomas. In vitro investigations using human cell lines did not show any clues in support of carcinoma formation. Instead, the DPP-4 inhibitory action of sitagliptin serves in other complications associated with T2DM. In any tissue injury due to hypoxic stress in T2DM, sitagliptin serves in the tissue repair mechanisms via its DPP-4 inhibiting property. Consequently, DPP-4, for not being able to be active in presence of sitagliptin, fails to truncate the CXCL-12/SDF-1 and therefore helps in the homing of HPCs/EPCs to repair the injured tissue. In conclusion, it can be said that more research is definitely required to be confirmed about the pre-cancerous activity of the drug, and to make the drug more usable in favour of the other beneficial effects of it.