The PAM gene encodes the sole enzyme responsible for amidating bioactive hormones, including GLP-1, and harbors two hypomorphic T2D-risk alleles (p.D563G and p.S539W); however, whether PAM regulates GLP-1, a key amidated incretin hormone, and whether this influences response to GLP-1 receptor agonist (GLP-1RA) therapy, remains unknown. Here, GLP1R is linked to type 2 diabetes mellitus.