Glucagon-like peptide 1-based therapies for type 2 diabetes: a focus on exenatide. Clin Diabetes

Glucagon-like peptide 1 (GLP-1)is produced by the proglucagongene in L-cells of the small intestine in response to nutrients.1 It stimulates glucose-dependent insulin release from the pancreatic islets. In addition to its insulinotropic effects, it is thought to exert antihyperglycemic effects by slowing gastric emptying,2 inhibiting inappropriate glucagon release,3 stimulating -cell proliferation4 and differentiation,5 and improving satiety.6 GLP-1 secretion is decreased in type 2 diabetes, thus making it a logical target for novel treatments of type 2 diabetes.7 In clinical trials, GLP-1 effects are evi-dent regardless of the duration or severi-ty of diabetes.8 Thus, modulating GLP-1 levels and GLP-1 activity through administration of the native hormone, analogs, and mimetics or by inhibiting its degradation has become a major focus of investigation for treating type 2 diabetes over the past decade. Exenatide is a GLP-1 mimetic, a synthetic form of the naturally occurring reptilian hormone exendin-4. It has been submitted for review by the Food and Drug Administration and could become available on the U.S. market by mid