What restrictions are there in the therapeutic use of GLP and how were they overcome

GLP-1 is destroyed by the enzymes of the gastrointestinal tract (since it is a protein) and by the enzyme dipeptidyl-peptidase IV (DPP-IV) in the blood in a few minutes. Consequently, it cannot be given by mouth. A continuous infusion (intravenous or subcutaneous) is not very practical.

For this reason, its molecule was subjected to chemical transformations, so that it can resist degradation by DPP-IV and act for a longer time. Such GLP-1 analogues are now in clinical trials (with very promising results), with the first agent of the class already having been approved.

The administration of DPP-IV inhibitors (small molecules that enhance the action of endogenous GLP-1 by inhibiting its degradation) has also been tried, so that its action can be prolonged.

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