Liraglutide and Colesevelam Changes Serum and Fecal Bile Acid Levels in a Randomized Trial with Patients with Bile Acid Diarrhea.

Autor:	Ellegaard AM; Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Kårhus ML; Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark., Krych L; Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark., Sonne DP; Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Forman JL; Section of Biostatistics, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hansen SH; Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark., Dragsted LO; Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark., Nielsen DS; Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark., Knop FK; Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Steno Diabetes Center Copenhagen, Herlev, Denmark.
Jazyk:	angličtina
Zdroj:	Clinical and translational gastroenterology [Clin Transl Gastroenterol] 2024 Sep 23. Date of Electronic Publication: 2024 Sep 23.
DOI:	10.14309/ctg.0000000000000772
Abstrakt:	Introduction: Both liraglutide and colesevelam improve bile acid diarrhea (BAD) symptoms. Colesevelam binds excess amounts of diarrhea-causing bile acids in the colon whereas the mode of action for liraglutide remains elusive. Here, we examined the impact of colesevelam and liraglutide treatment on the concentrations of bile acids in serum and feces and the fecal microbiota composition to better understand the two drugs' modes of action. Methods: Bile acid species were analyzed in serum and fecal samples from a randomized, double-blind, double-dummy trial at baseline and after three and six weeks of orally administered colesevelam (1,875 mg twice daily, n = 26) or subcutaneously administered liraglutide (uptitrated by weekly increments of 0.6 mg from 0.6 to 1.8 mg daily, n = 26) in patients with 75selenium-homotaurocholic acid test-verified, idiopathic, or post-cholecystectomy BAD. Fecal microbiota composition was analyzed by 16S rRNA gene amplicon sequencing at the same time points. Results: Colesevelam increased the fecal concentrations of all bile acid species while it decreased serum concentrations of secondary bile acids. Liraglutide induced a small increase in serum unconjugated bile acid concentrations without affecting fecal bile acid concentrations. No changes in fecal microbiota composition were observed with either treatment. Conclusion: Colesevelam and liraglutide exhibit distinct effects on serum and fecal bile acid concentrations with colesevelam reducing serum concentrations of secondary bile acids and promoting fecal bile acid excretion while liraglutide enhances serum concentrations of unconjugated bile acids, potentially through deceleration of small intestinal transit time allowing more time for passive absorption of bile acids. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)
Databáze:	MEDLINE
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