Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins that stimulate insulin secretion from pancreatic β cells in response to food ingestion. Modified GLP-1 and GIP peptides are potent agonists for their incretin receptors, and some evidence shows that the dual GLP-1 and GIP receptor agonist tirzepatide is effective in promoting marked weight loss. GLP-1 receptor agonists signal in the CNS to suppress appetite, increase satiety, and thereby decrease calorie intake, but many other effects of incretin signalling have been recognised that are relevant to the treatment of non-alcoholic fatty liver disease (NAFLD). This Review provides an overview of the literature supporting the notion that endogenous incretins and incretin-receptor agonist treatments are important not only for decreasing risk of developing NAFLD, but also for treating NAFLD and NAFLD-related complications. We discuss incretin signalling and related incretin-receptor agonist treatments, mechanisms in key relevant tissues affecting liver disease, and clinical data from randomised controlled trials. Finally, we present future perspectives in this rapidly developing field of research and clinical medicine.

10.1016/S2468-1253(22)00338-7

2468-1253

179-191

Targher, Giovanni

ede6ba46-76bf-4b2a-a139-760df830bf67

Mantovani, Alessandro

604704bf-8d6e-4140-b69b-36559caa7027

Byrne, Christopher

1370b997-cead-4229-83a7-53301ed2a43c

February 2023

Targher, Giovanni

ede6ba46-76bf-4b2a-a139-760df830bf67

Mantovani, Alessandro

604704bf-8d6e-4140-b69b-36559caa7027

Byrne, Christopher

1370b997-cead-4229-83a7-53301ed2a43c

Targher, Giovanni, Mantovani, Alessandro and Byrne, Christopher (2023) Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease. The Lancet Gastroenterology & Hepatology, 8 (2), 179-191. (doi:10.1016/S2468-1253(22)00338-7).

Record type: Review

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Accepted/In Press date: 29 September 2022

e-pub ahead of print date: 5 January 2023

Published date: February 2023

Additional Information: Please note title change from original title: Glucagon-like peptide 1 receptor agonists and other incretin receptor agonists: mechanisms and possible hepatoprotective effects in non-alcoholic fatty liver disease.