P104

P104 is a selective peptide agonist of the vasoactive intestinal polypeptide receptor 2 (VPAC2), developed by Eli Lilly for the potential treatment of type 2 diabetes. VPAC2 is a class B G-protein coupled receptor highly expressed in pancreatic beta-cells, where its activation potently enhances glucose-dependent insulin secretion. Unlike non-selective agonists such as pituitary adenylate cyclase-activating polypeptide (PACAP), P104 selectively targets VPAC2 without activating VPAC1, thereby avoiding the stimulation of glucagon release. In preclinical animal models, P104 has demonstrated the ability to significantly enhance insulin secretion, improve plasma lipid levels, and reduce food intake, making it a promising candidate for metabolic regulation.