Engaging the Gears of GLP-1: Incretin Hormones in the Treatment of Type 2 Diabetes

Corporate-sponsored Symposium
Supported by an unrestricted educational grant from Amylin Pharmaceuticals, Inc and Eli Lilly and Company
Sunday, June 12, 2005
5:30 - 8:00 PM

Faculty
Robert R Henry, MD
Daniel J Drucker, MD
Lawrence Blonde, MD, FACP, FACE
Deborah Hinnen, APRN, DB-ADM, CDE, FAAN

Reported by Joelle Escoffery, PhD

The incretin hormones are produced by the GI tract in response to nutrient intake. The incretin effect refers to the enhanced insulin response to oral, as compared with intravenous, glucose intake. The 2 primary incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). GLP-1 secretion is impaired in type 2 diabetes, but response to exogenous GLP-1 administration is preserved, making it an attractive therapeutic target. GLP-1 has a number of beneficial effects, including stimulation of glucose-dependent insulin secretion, suppression of glucagon secretion, delay of gastric emptying, and beta-cell stimulation.

Native GLP-1 is rapidly degraded by dipeptidyl peptidase-IV (DPP-IV). Accordingly, two approaches increasing circulating levels of GLP-1 are currently being explored: the identification of GLP-1 receptor agonists that are resistant to DPP-IV or inhibiting DPP-IV. Clinical research has demonstrated positive effects of both approaches on improving glycemic control and suppressing postprandial glucagon production. Further, the GLP-1 receptor agonists have shown consistent weight loss, whereas the DPP-IV inhibitors are weight neutral. The primary side effects of the GLP-1 receptor agonists are usually mild to moderate and gastrointestinal in nature. It is important to note that the effect of the GLP-1 receptor agonists on weight is independent of the observed GI side effects.

Now that the first GLP-1 receptor agonist, exenatide, is available for clinical use, practical clinical information and several case studies were also presented. Exenatide is delivered via a pen injection. The pens are prefilled and contain 60 fixed doses of either 5 mcg or 10 mcg (30 day supply). Exenatide should be taken twice daily within 60 minutes of a meal. This treatment is indicated for use among patients with type 2 diabetes failing therapy with sulfonylurea monotherapy, metformin monotherapy, or metformin and sulfonylurea combination. In particular, it may be a beneficial therapeutic strategy earlier in the disease process, among patienst with A1C < 8.5, and among patients with elevated postprandial glucose levels. The case studies presented mirrored findings from the published clinical trials. Patients taking exenatide lost weight and improved glycemic control, with some mild nausea present very early in the course of treatment. Educational considerations with exenatide include the following:

• Monitoring after meals to ensure that the therapy is effective
• Possible need to reduce sulfonylurea dose to avoid hypoglycemia
• If an injection is missed, simply take the next dose at the prescribed time, but do not double dose
• Exenatide should be kept cool