Gliptins

CORRISPONDENCE: As stated by Daniel Drucker and Michael Nauck,1 inhibitors of dipeptidyl peptidase 4 (DPP-4, “gliptins”) have been introduced into clinical practice for their ability to cleave and inactivate glucagon-like peptide 1 (GLP-1) and stimulate insulin secretion in type 2 diabetes mellitus. Another interesting property of DPP-4 is potent inactivation of the chemokine CXCL12.2, 3 and 4 CXCL12 is thought to be central in the homing of haemopoietic stem cells (HSC) to bone marrow. By lowering CXCL12 catabolism, DPP-4 inhibition with gliptins is a promising strategy by which to improve HSC homing and increase engraftment efficiency after bone marrow transplantation. Preclinical models with other DPP-4 inhibitors5 support this notion. Now, for the first time, haematologists have clinically approved DPP-4 inhibitors in their armamentarium. But clinical trials of gliptins have focused on diabetic patients and have not investigated their effect on HSC trafficking. Reduction in HSC counts in peripheral blood would be an expected consequence of diminished CXCL12 inactivation by DPP-4 after gliptin treatment. We do not know whether this effect occurs nor the concentrations of drug required to achieve it, so future clinical trials in recipients of HSC transplants should investigate this strategy. Conversely, it might be wise to avoid gliptins during treatment with granulocyte-colony stimulating factor for HSC mobilisation, in which the reverse of homing is desired. We declare that we have no conflict of interest.