On the treatment of diabetes mellitus with glucagon-like peptide-1.

As a therapeutic principle, the insulinotropic peptide, GLP-1, of the secretin-glucagon family of peptides, has turned out to possess some remarkably attractive properties, including the capability of normalizing blood glucose concentrations in patients with non-insulin-dependent diabetes mellitus and promoting satiety and reducing food intake in healthy volunteers. Because of rapid and extensive metabolization, the peptide is not immediately clinically applicable and, as a therapeutic principle, GLP-1 is still in its infancy. Some possible avenues for circumventing these difficulties are the development of DPP-IV-resistant analogs, the inhibition of DPP-IV, enhancement of GLP-1 secretion, GLP delivery systems using continuous subcutaneous infusion or buccal tablets, GLP-1 absorption, and orally active, stable analogs. It seems likely that one or more of these approaches could result in a clinically useful development program.