Glucagon-like peptide-1 agonists (exenatide): consensus statement published on Diabetes Care

Below is a transcript of the latest statement (December 2008) published on Diabetes Care, about the role of Glucagon-like peptide-1 agonists (exenatide) in the medical management of hyperglycemia in type 2 diabetes.

Glucagon-like peptide-1 agonists (exenatide).

Glucagon-like peptide-1 (GLP-1) 7–37, a naturally occurring peptide produced by the L-cells of the small intestine, potentiates glucose-stimulated insulin secretion. Exendin-4 has homology with the human GLP-1 sequence but has a longer circulating half-life. It binds avidly to the GLP-1 receptor on the pancreatic beta-cell and augments glucose-
mediated insulin secretion (32). Synthetic exendin-4 (exenatide) was approved for use in the U.S. in 2005 and is administered twice per day by subcutaneous injection. Although there are less published data on this new compound than the other blood glucose–lowering medications, exendin-4 appears to lower A1C levels by 0.5–1 percentage points, mainly by lowering postprandial blood glucose levels (78–81).

Exenatide also suppresses glucagon secretion and slows gastric motility. It is not associated with hypoglycemia but causes a relatively high frequencyof gastrointestinal disturbances, with 30-45% of treated patients experiencing one or more episodes of nausea, vomiting, or diarrhea (78–81). These side effects tend to abate over time. In published trials, exenatide is associated with weight loss of aprox.  2–3 kg over 6 months, some of which may be a result of its gastrointestinal side effects. Recent reports have suggested a risk for pancreatitis associated with use of GLP agonists; however, the number of cases is very small and whether the relationship is causal or coincidental is not clear at this time.

Currently, exenatide is approved for use in the U.S. with sulfonylurea, metformin, and/or a TZD.

Several other GLP-1 agonists and formulations are under development

Free full text: Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. Diabetes Care 31:1–11, 2008

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