An update on peptide-based therapies for type 2 diabetes and obesity

Clifford J Bailey, Peter R Flatt, J Michael Conlon

Research output: Contribution to journalArticlepeer-review

Abstract

Long-acting analogues of the naturally occurring incretin, glucagon-like peptide-1 (GLP-1) and those modified to interact also with receptors for glucose-dependent insulinotropic polypeptide (GIP) have shown high glucose-lowering and weight-lowering efficacy when administered by once-weekly subcutaneous injection. These analogues herald an exciting new era in peptide-based therapy for type 2 diabetes (T2D) and obesity. Of note is the GLP-1R agonist semaglutide, available in oral and injectable formulations and in clinical trials combined with the long-acting amylin analogue, cagrilintide. Particularly high efficacy in both glucose- and weight lowering capacities has also been observed with the GLP-1R/GIP-R unimolecular dual agonist, tirzepatide. In addition, a number of long-acting unimolecular GLP-1R/GCGR dual agonist peptides and GLP-1R/GCGR/GIPR triagonist peptides have entered clinical trials. Other pharmacological approaches to chronic weight management include the human monoclonal antibody, bimagrumab which blocks activin type II receptors and is associated with growth of skeletal muscle, an antibody blocking activation of GIPR to which are conjugated GLP-1R peptide agonists (AMG-133), and the melanocortin-4 receptor agonist, setmelanotide for use in certain inherited obesity conditions. The high global demand for the GLP-1R agonists liraglutide and semaglutide as anti-obesity agents has led to shortage so that their use in T2D therapy is currently being prioritized. [Abstract copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.]
Original languageEnglish
Article number170939
Number of pages6
JournalPeptides
Volume161
Early online date3 Jan 2023
DOIs
Publication statusE-pub ahead of print - 3 Jan 2023

Bibliographical note

© 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Keywords

  • Glucagon
  • Type 2 diabetes
  • Semaglutide
  • GLP-1
  • Cagrilintide
  • GIP
  • Tirzepatide
  • Obesity

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