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

 

Authors Wang L 

Received 26 January 2022

Accepted for publication 18 May 2022

Published 25 May 2022 Volume 2022:16 Pages 1547—1559

DOI https://doi.org/10.2147/DDDT.S358989

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Tin Wui Wong

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