The incretin hormones are released during meals from gut endocrine cells. They potentiate glucose-induced insulin secretion and may be responsible for up to 70 % of postprandial insulin secretion and for 80 % of glucose clearance. The incretin hormones include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) both of which may also promote proliferation/neogenesis of b-cells and prevent their decay (apoptosis). Both hormones contribute to insulin secretion from the beginning of a meal and their effects are progressively amplified as plasma glucose concentrations rise. The current interest in the incretin hormones is due to the fact that the incretin effect is severely reduced or absent in patients with type 2 diabetes (T2DM). In addition, there is hyperglucagonemia, which is not suppressible by glucose. In such patients, the secretion of GIP is near normal, but its effect on insulin secretion, particularly the late phase, is severely impaired. The loss of GIP action is probably a consequence of diabetes, since it is also observed in patients with diabetes secondary to chronic pancreatitis, in whom the incretin effect is also lost. GLP-1 secretion, on the other hand, is also impaired, but its insulinotropic and glucagon-suppressive actions are preserved although the potency of GLP-1 in this respect is decreased compared to healthy subjects. However, in supraphysiological doses, GLP-1 administration may completely normalize b as well as a-cell sensitivity to glucose. The impaired action of GLP-1 and GIP in T2DM may be at least partly restored by improved glycemic control as shown in studies involving 4 weeks of intensive insulin therapy. The reduced incretin effect may contribute to impaired regulation of insulin and glucagon secretion in T2DM, and, in support of this, exogenous GLP-1 administration may restore blood glucose regulation to near normal levels. Thus, the pathogenesis of T2DM seems to involve a dysfunction of both incretins. Enhancement of incretin action with GLP-1 may therefore represent a therapeutic solution. In addition to its effects on a- and b-cells, GLP-1 also seems to exert a protective effect of GLP-1 on b-cells. It is probably also a physiological regulator gastric emptying as well as appetite and food intake. GLP-1 therefore has numerous antidiabetic actions and these form the basis for several new therapeutic agents, which haven proven effective in the treatment of T2DM. There is also evidence that the actions of GLP-1 may be responsible for some of the effects of gastric bypass operations of body weight and T2DM.