GLP-1 receptor agonist (revision 2)

A GLP-1 receptor agonist (GLP-1 RA) is a drug that activates the GLP-1 receptor, reproducing and prolonging the actions of the endogenous incretin hormone Glucagon-like peptide-1. The class was developed for type 2 diabetes and has since been approved, for several of its members, for the treatment of obesity and for reduction of cardiovascular risk.^[1]

Native GLP-1 is unusable as a medicine because Dipeptidyl peptidase-4 inactivates it within one to two minutes of secretion. Every clinically successful agonist therefore solves the same engineering problem in one of a small number of ways: substitution of the residue attacked by the protease, fatty-acid acylation that ties the molecule to serum albumin, fusion to an immunoglobulin fragment, or use of a naturally protease-resistant scaffold such as exendin-4.^[2]