Designing a Dual GLP-1R/GIPR Agonist from Tirzepatide: Comparing Residues Between Tirzepatide, GLP-1, and GIP

Abstract: Improving type 2 diabetes using incretin analogues is becoming increasingly plausible. Currently, tirzepatide is the most promising listed incretin analogue. Here, I briefly explain the evolution of drugs of this kind, analyze the residue discrepancies between tirzepatide and endogenous incretins, summarize some existing strategies for prolonging half-life, and present suggestions for future research, mainly involving biased functions. This review aims to present some useful information for designing a dual glucagon like peptide-1 receptor/glucose-dependent insulinotropic polypeptide receptor agonist. Keywords: tirzepatide, GLP-1, GIP, Aib, structure–activity relationship, structure–function relationship