Dipeptidyl peptidase-IV (DPP-IV) is an enzyme responsible for the inactivation of the glucoregulatory incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In this report, we show that the hypolipidemic agent atorvastatin is a competitive inhibitor of porcine DPP-IV in vitro, with K(i)=57.8+/-2.3 microM. These results may have implications in the development of novel DPP-IV inhibitors based on the use of atorvastatin as a lead compound for the treatment of type 2 diabetes.