Glucagon-like peptide-1 (GLP-1) is a member of the incretin family of neuroendocrine peptide hormones secreted from L-cells of the intestine in response to food ingestion. A key function of GLP-1 is to activate its receptor, GLP-1R, on the pancreatic β-cell to enhance glucose-dependent insulin secretion. Unfortunately, the rapid proteolysis of GLP-1 in blood limits its use as a therapeutic agent, thus prompting the development of GLP-1 analogs with enhanced resistance. Validation of GLP-1R agonists as a therapeutic modality was achieved by Exendin-4 (Byetta), a peptide GLP-1 receptor agonist recently approved for the treatment of Type II diabetes mellitus. Byetta posted 2007 sales of US$ 636 mln making GLP-1R an attractive target. As Exendin-4 is administered by twice daily subcutaneous administration there is ample space for improving the convenience of administering a GLP-1R agonist. The pipeline of novel GLP-1 agonists is rather full with seven different compounds in phase II or III trials and further ten projects in phase I. Technologies to improve the convenience of administration include sustained release formulations, fusion protein and bonding technology, nasal and inhalation delivery as well as oral approaches for peptides and small molecules. Product details

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