Inhibition of multifunctional dipeptidyl peptidase-IV: is there a risk of oncological and immunological adverse effects?

Abstract

Inhibitors of dipeptidyl peptidase-IV (DPP-IV) are a novel class of anti-diabetes drugs; inhibiting the breakdown of incretins, they increase their biological availability and decrease thus blood glucose levels. However, in addition to regulating glucose homeostasis, DPP-IV has many diverse functions, such as modulating cell growth, differentiation and transformation and immune function. Within the immune system, DPP-IV exerts mainly stimulating effects, while its relation to malignancies is highly variable. Therefore, long-term inhibition of this enzyme could have serious side effects including immune dysregulation or increased risk of cancer. Although the data on the effects of DPP-IV inhibitors in humans are scarce, the increased risk of infections and the tendency towards a higher incidence of some tumours fall in line with experimental evidence suggesting the possibility of their adverse immunological and oncological effects. Further research is obviously needed to clarify the effector mechanisms of DPP-IV inhibitors on immune function and tumour biology. Most important, however, is obtaining reassuring safety data from adequately powered, long-term trials of DPP-IV inhibitors in humans. In the meantime, all the potential risks of DPP-IV inhibitors should be kept in mind, and this class of drugs needs to be regarded with some degree of caution.