triagonist 13

Triagonist 13 is a unimolecular peptide-protein conjugate designed to simultaneously activate the insulin receptor, the glucagon-like peptide-1 receptor (GLP-1R), and the glucagon receptor (GCGR). Developed by Eli Lilly, this compound aims to provide enhanced glycemic control and weight loss for the treatment of diabetes and obesity. The molecule is synthesized by conjugating an insulin moiety to a GLP-1R/GCGR coagonist peptide using alkyne-azide click chemistry, specifically at the insulin B1F position and position 24 of the coagonist. Preclinical evaluations in rat and minipig models demonstrated that Triagonist 13 possesses insulin-like glucose-lowering activity comparable to insulin degludec, complemented by the metabolic benefits of GLP-1 and glucagon agonism.