Incretins are a type of gastrointestinal hormone that cause an increase in the amount of insulin released from the beta cells of the islets of Langerhans after eating, even before blood glucose levels become elevated. They also slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. As expected, they also inhibit glucagon release from the alpha cells of the Islets of Langerhans. The two main candidate molecules that fulfil criteria for an incretin are glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (aka glucose-dependent insulinotropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4).

GLP-1 (7-36) amide is not very useful for treatment since it must be administered by continuous subcutaneous infusion. Several long-lasting analogs that have insulinotropic activity have been developed and one, exenatide, has been approved for use in the U.S. The main disadvantage of these GLP-1 analogs is that they must be administered by subcutaneous injection.

Another approach is to inhibit the enzyme that inactivates GLP-1 and GIP, DPP-4. Several DPP-4 inhibitors that can be taken orally as a tablet have been developed. One of them, Januvia (sitagliptin) was approved by the FDA on October 18, 2006.