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28-03-2023 | Obesity | Review

The expanding incretin universe: from basic biology to clinical translation

Authors: Daniel J. Drucker, Jens J. Holst

Published in: Diabetologia | Issue 10/2023

Abstract

Incretin hormones, principally glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(GLP-1), potentiate meal-stimulated insulin secretion through direct (GIP + GLP-1) and indirect (GLP-1) actions on islet β-cells. GIP and GLP-1 also regulate glucagon secretion, through direct and indirect pathways. The incretin hormone receptors (GIPR and GLP-1R) are widely distributed beyond the pancreas, principally in the brain, cardiovascular and immune systems, gut and kidney, consistent with a broad array of extrapancreatic incretin actions. Notably, the glucoregulatory and anorectic activities of GIP and GLP-1 have supported development of incretin-based therapies for the treatment of type 2 diabetes and obesity. Here we review evolving concepts of incretin action, focusing predominantly on GLP-1, from discovery, to clinical proof of concept, to therapeutic outcomes. We identify established vs uncertain mechanisms of action, highlighting biology conserved across species, while illuminating areas of active investigation and uncertainty that require additional clarification.

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Title: The expanding incretin universe: from basic biology to clinical translation
Authors: Daniel J. Drucker
Jens J. Holst
Publication date: 28-03-2023
Publisher: Springer Berlin Heidelberg
Keywords: Obesity
Obesity
Insulins
Heart Failure
Insulins
Type 2 Diabetes
Published in: Diabetologia / Issue 10/2023
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-023-05906-7

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Obesity Clinical Trial Summary

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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

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