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‐dependant 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. In a previous publication, 1 we introduced the new incretin hormone, glucagon‐like peptide‐1 and presented its effects on blood glucose regulation in normal and diabetic subjects. Its role as an incretin hormone, being the most potent insulinotropic hormone known, was emphasized, and it was described how intravenous infusions of GLP‐1 can completely normalize the hyperglycemia of patients with non‐insulin‐dependent diabetes mellitus (NIDDM). It was concluded that GLP‐1 had great potential as a therapeutic agent. The present communication deals with the attempts that have been made to transform this typical peptide hormone of the glucagon‐secretin‐VIP‐PACAP family into a clinically useful therapeutic agent.