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Open Access 20-05-2023 | Obesity | Review

Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy

Authors: Matthias Tschöp, Ruben Nogueiras, Bo Ahrén

Published in: Diabetologia | Issue 10/2023

Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are established pharmaceutical therapies for the treatment of type 2 diabetes and obesity. They mimic the action of GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also reduce body weight by inducing satiety through central actions. The GLP-1 receptor agonists used clinically are based on exendin-4 and native GLP-1 and are available as formulations for daily or weekly s.c. or oral administration. GLP-1 receptor agonism is also achieved by inhibitors of dipeptidyl peptidase-4 (DPP-4), which prevent the inactivation of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), thereby prolonging their raised levels after meal ingestion. Other developments in GLP-1 receptor agonism include the formation of small orally available agonists and compounds with the potential to pharmaceutically stimulate GLP-1 secretion from the gut. In addition, GLP-1/glucagon and GLP-1/GIP dual receptor agonists and GLP-1/GIP/glucagon triple receptor agonists have shown the potential to reduce blood glucose levels and body weight through their effects on islets and peripheral tissues, improving beta cell function and stimulating energy expenditure. This review summarises developments in gut hormone-based therapies and presents the future outlook for their use in type 2 diabetes and obesity.

Graphical Abstract

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Title: Gut hormone-based pharmacology: novel formulations and future possibilities for metabolic disease therapy
Authors: Matthias Tschöp
Ruben Nogueiras
Bo Ahrén
Publication date: 20-05-2023
Publisher: Springer Berlin Heidelberg
Keywords: Obesity
Obesity
Incretin Mimetics
Incretin Mimetics
Tirzepatide
Semaglutide
Type 2 Diabetes
Published in: Diabetologia / Issue 10/2023
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-023-05929-0

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