Incretins and Type 2 Diabetes

Presented by Riccardo Perfetti, MD, PhD
Workshop A
Thursday, October 28, 2004

Reviewed by Joelle Escoffery, PhD

The “incretin effect” refers to the discovery that oral glucose is more effective than intravenous glucose at stimulating insulin secretion. The incretin hormones have been shown to enhance glucose-dependent insulin secretion. Although there are several incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for 90% of the incretin effect.

GLP-1 is an incretin hormone that has been shown to enhance insulin secretion, suppress glucagon secretion, induce satiety, and delay gastric emptying, making it an attractive potential therapeutic agent. Further, it has also been associated with improved markers of β-cell function. However, native GLP-1 is rapidly degraded by dipeptidase peptidyl-IV (DPP-IV), so continuous intravenous infusion would be required if native GLP-1 were to be used. Two potential strategies are currently being explored to extend the half-life of GLP-1, including: 1) the use of GLP-1 receptor agonists that resist DPP-IV degradation, and 2) the use of therapeutic agents that inhibit the in vivo action of DPP-IV. A number of GLP-1 receptor agonists and DPP-IV inhibitors are currently under investigation. GLP-1 receptor agonists include exenatide, liraglutide, DAC-GLP-1, and AVE-0010. The DPP-IV inhibitor LAF237 is also being investigated.