PuSH - Publication Server of Helmholtz Zentrum München

Nogueiras, R.* ; Nauck, M.A.* ; Tschöp, M.H.

Gut hormone co-agonists for the treatment of obesity: From bench to bedside.

Nat. Metab. 5, 933-944 (2023)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The discovery and development of so-called gut hormone co-agonists as a new class of drugs for the treatment of diabetes and obesity is considered a transformative breakthrough in the field. Combining action profiles of multiple gastrointestinal hormones within a single molecule, these novel therapeutics achieve synergistic metabolic benefits. The first such compound, reported in 2009, was based on balanced co-agonism at glucagon and glucagon-like peptide-1 (GLP-1) receptors. Today, several classes of gut hormone co-agonists are in development and advancing through clinical trials, including dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) co-agonists (first described in 2013), and triple GIP-GLP-1-glucagon co-agonists (initially designed in 2015). The GLP-1-GIP co-agonist tirzepatide was approved in 2022 by the US Food and Drug Administration for the treatment of type 2 diabetes, providing superior HbA1c reductions compared to basal insulin or selective GLP-1 receptor agonists. Tirzepatide also achieved unprecedented weight loss of up to 22.5%-similar to results achieved with some types of bariatric surgery-in non-diabetic individuals with obesity. In this Perspective, we summarize the discovery, development, mechanisms of action and clinical efficacy of the different types of gut hormone co-agonists, and discuss potential challenges, limitations and future developments.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Glucagon-like Peptide-1; Glp-1 Receptor Agonist; Gastric-inhibitory Polypeptide; Dependent Insulinotropic Polypeptide; Glycemic Control; Food-intake; Weight-loss; Dual Gip; Corrects Obesity; Energy-intake
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Journal Nature metabolism
Quellenangaben Volume: 5, Issue: 6, Pages: 933-944 Article Number: , Supplement: ,
Publisher Springer
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)