Bile acid-farnesoid X receptor-fibroblast growth factor 19 axis in patients with short bowel syndrome: The randomized, glepaglutide phase 2 trial
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Hvistendahl et al_Journal of Parenteral and Enteral Nutrition_2021_e2224_(Accepted manuscript)
Accepteret manuskript, 1.000 KB, PDF-dokument
Background: The gut-liver axis and enterohepatic circulation have gained increasing attention lately. Patients with short bowel syndrome (SBS) are, in fact, human knock-out models that may assist in the understanding of bile acid synthesis and regulation. We evaluated effect of glepaglutide (a long-acting glucagon-like peptide-2 analog) on bile acid synthesis (the enterohepatic circulation of bile acids and liver biochemistry in patients with SBS.
Method: In a single-center, double-blinded, dose-finding, crossover phase 2 trial, 18 patients with SBS were randomly assigned to 2 of 3 treatment arms (0.1, 1 and 10 mg) with daily subcutaneous injections of glepaglutide for 3 weeks. The washout period between the 2 treatment periods was 4-8 weeks. Measurements were performed at baseline and at the end of each treatment period and included postprandial plasma samples for fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4), total excretion of fecal bile acids, gene expression of farnesoid X receptor (FXR) in intestinal mucosal biopsies, total plasma bile acids, and liver biochemistry.
Results: Compared to baseline, the median (interquartile range) postprandial response (area under the curve 0-2h) of FGF19 increased by 150 h × ng/L (41, 195; P = 0.001) and C4 decreased by 82 h × μg/L (-169, -28; P = 0.010) in the 10-mg dose. FXR gene expression did not change in any of the groups. Alkaline phosphatase significantly decreased.
Conclusions: Glepaglutide may stimulate the bile acid/FXR/FGF19 axis, leading to increased plasma concentrations of FGF19. Thereby, glepaglutide may ameliorate the accelerated de novo bile acid synthesis and play a role in the prevention and/or treatment of intestinal failure-associated liver disease.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Journal of Parenteral and Enteral Nutrition |
Vol/bind | 46 |
Udgave nummer | 4 |
Sider (fra-til) | 923-935 |
Antal sider | 13 |
ISSN | 0148-6071 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
CURIS 2022 NEXS 139
This article is protected by copyright. All rights reserved.
- Det Natur- og Biovidenskabelige Fakultet
Forskningsområder
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 275377155