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The observation that an oral glucose load is more effective at releasing insulin, compared with the same amount of glucose given intravenously, has been called the incretin effect, and is due to the augmentation of glucose-stimulated insulin secretion by intestinally derived peptides.Glucagon-like peptide-1 (GLP-1), in particular, has been shown to stimulate insulin release in a glucose-dependent manner in humans, but it is rapidly metabolised by dipeptidyl-peptidase-4 (DPP-4). Inhibition of DPP-4 activity enhances fasting and post-prandial GLP-1 which, in turn, improves glycaemic control by increasing glucose-dependent insulin secretion and by decreasing glucagon concentration.Current oral antidiabetic drugs (OADs) for type 2 diabetes are limited by adverse effects such as gastrointestinal problems, weight gain, oedema, or hypoglycaemia. In addition, there are recent concerns about rosiglitazone and cardiovascular outcomes, and with the thiazolidinediones in general regarding excess fracture rate in women and increased risk of heart failure. Thus the introduction of a new class of OADs, the DPP-4 inhibitors, is welcome.This review article discusses the most clinically relevant data published on DPP-4 inhibitors based on Medline literature searches (1966 to August 2007) and posters and oral presentations from the American Diabetes Association Scientific Sessions in 2006 and 2007. We have concentrated our review on two DPP-4 inhibitors: sitagliptin (Januvia) and vildagliptin (Galvus).