We propose that an altered incretin response, probably due to impaired interaction of nutrients with the gut mucosa due to thickened secretions, may play a role in the development of the disease. Specifically, low GIP and GLP-1, may explain the poor β-cell function observed in these patients prior to CFRD appearance. These incretins have known trophic effects on β-cells, and thus their lower levels may contribute to the development of quantitative as well as qualitative defects in β-cell function and thus may lead to the development of CFRD. Thus, increasing levels of these incretins using a DPP-IV inhibitor may improve glucose metabolism and delay/prevent the development of CFRD.