The incretin effect describes the phenomenon that an oral glucose load gives rise to a greater insulin secretion than an intravenous glucose load given to obtain identical glucose profiles during the two loads socalled isoglycaemia. The incretin effect is mediated by two gut hormones released in response to nutrients Glucose-dependent insulinotropic polypeptide GIP and Glucagon-like peptide 1 GLP- 1. The incretin effect has the important physiological importance to modify insulin secretion during a meal so that blood glucose concentrations are kept within normal limits. The incretin effect is markedly reduced in type 2 diabetes mellitus so that insulin secretion is almost similar after oral and intravenous glucose. This is caused by a decreased secretion of GLP-1 in response to a meal, a decreased sensitivity of GLP-1 on the diabetic beta-cells and a complete loss of late-phase insulin secretion in response to GIP. The defects of the incretin hormones on the pancreatic beta-cells seems to be an early defect at the onset of diabetes and has been suggested to be caused by the diabetic state as a secondary event rather than a primary pathogenic event. Thus, the effect of the incretin hormones can be improven by four weeks of near normalisation of blood glucose in type 2 diabetics. Since GLP-1 in contrast to GIP have an effect on the diabetic beta-cells a GLP-1 based therapy has been developed and this has given rise to a completely new treatment modality of type 2 diabetes with GLP-1 agonists.