Dipeptidyl Peptidase-4 Inhibitors - Risks and Side Effects

Risks and Side Effects

Long-term effects of DPP-4 inhibitors on mortality and morbidity are so far inconclusive, although adverse effects, including nasopharyngitis (the common cold), headache, nausea, hypersensitivity and skin reactions, have been observed in clinical studies. Consistent with this FDA approval of Novartis' DPP-4 inhibitor vildagliptin (Galvus®) was delayed because of skin lesions with blistering observed in nonhuman primate toxicology studies; one year later, Novartis CEO Dan Vasella remained uncertain as to their ability to ever file to market the drug in the United States. Other possible adverse effects, including hypersensitivity reactions and pancreatitis, have been reported. These effects may relate to DPP-4's function in restricting the inflammatory actions of the chemokine CCL11/eotaxin, so that inhibiting DPP-4 might unleash the recruitment of inflammatory cells.

Although one in vitro study found that DPP-4 inhibitors, together with GLP-2, increased proliferation and migration of colon cancer cells, which might encourage cancer cells to metastasize, carcinogenicity has not been confirmed in long-term, preclinical studies of the major DPP-4 inhibitors.