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Bispebjerg Hospital - a part of Copenhagen University Hospital

Bile acid - farnesoid X receptor - fibroblast growth factor 19 axis in patients with short bowel syndrome: the randomized glepaglutide phase 2 trial

Research output: Contribution to journalJournal articlepeer-review


  1. Liraglutide decreases postprandial fibroblast growth factor 19 and glucagon-like peptide 2, and increases postprandial cholecystokinin in individuals with obesity

    Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

  2. The glucose-lowering effect of the bile acid sequestrant sevelamer in patients with type 2 diabetes is not mediated by glucagon-like peptide 1

    Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

  3. The Glucagon-Like Peptide-1 Analog, Liraglutide Is a Safe and Effective Treatment of Bile Acid Malabsorption: A Proof of Concept Study

    Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

  4. The Glucose-Lowering Effect of the Bile Acid Sequestrant Sevelamer Is Not Mediated by Glucagon-Like Peptide-1

    Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

  • Mark Krogh Hvistendahl
  • Rahim Mohammad Naimi
  • Svend Høime Hansen
  • Jens Frederik Rehfeld
  • Hannelouise Kissow
  • Jens Pedersen
  • Lars Ove Dragsted
  • David Peick Sonne
  • Filip Krag Knop
  • Palle Bekker Jeppesen
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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 with 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.

CONCLUSION: 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.

Original languageEnglish
JournalJournal of Parenteral and Enteral Nutrition
Issue number4
Pages (from-to)923-935
Number of pages13
Publication statusPublished - May 2022

    Research areas

  • 7α-hydroxy-4-cholesten-3-one, fibroblast growth factor 19, glucagon-like peptide-2, short bowel syndrome

ID: 66872696