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BMC Cardiovascular Disorders

, 15:75

First Online: 22 July 2015Received: 24 February 2015Accepted: 14 July 2015DOI: 10.1186-s12872-015-0070-9

Cite this article as: Rudling, M., Camilleri, M., Graffner, H. et al. BMC Cardiovasc Disord 2015 15: 75. doi:10.1186-s12872-015-0070-9

Abstract

BackgroundElobixibat is a minimally absorbed ileal bile acid BA transporter IBAT inhibitor in development against chronic constipation CC and constipation-predominant Irritable Bowel Syndrome IBS-C. CC is associated with an increased risk for cardiovascular disease and type2 diabetes mellitus. The objectives of this study were to evaluate metabolic effects of elobixibat. Effects on plasma lipids and BA synthesis were evaluated utilizing a 4-week, placebo-controlled study in patients with dyslipidemia while changes of glucagon-like peptide-1 GLP-1 by elobixibat was assayed in samples from a 14 day high-dose elobixibat study in patients with CC.

MethodsThirty-six dyslipidemic patients, 21 females, mean age 63 years, were randomized to 2.5 mg or 5 mg elobixibat or placebo once daily for four weeks. The primary endpoint was the change in low density lipoprotein LDL cholesterol. Secondary endpoints included other lipid parameters and serum 7α-hydroxy-4-cholesten-3-one C4, a marker of BA bile acid synthesis. Another study, in 36 patients with CC treated with high dose elobixibat; 15 mg or 20 mg-day or placebo for 14 days, was evaluated for changes in GLP-1.

ResultsIn the dyslipidemia study LDL cholesterol was reduced by 7.4 % p = 0.044, and the LDL-HDL ratio was decreased by 18 % p = 0.004. Serum C4 increased, indicating that BA synthesis was induced. No serious adverse events were recorded. In the CC study, GLP-1 increased significantly in both the 15 mg 20.7 ± 2.4 pmol-L; p = 0.03 and the 20 mg group 25.6 ± 4.9 pmol-L; p = 0.02.

ConclusionsElobixibat reduces LDL cholesterol and LDL-HDL ratio and increase circulating peak GLP-1 levels, the latter in line with increased intestinal BA mediated responses in humans.

Trial registrationsClinicalTrial.gov: NCT01069783 and NCT01038687.

KeywordsDyslipidemia Elobixibat Glucagon-like peptide-1 GLP-1 Ileal bile acid BA transporter IBAT inhibitor AbbreviationsASBTApical sodium-dependent BA transporter

BABile acids

C47α-hydroxy-4-cholesten-3-one

CCChronic constipation

FXRFarnesoid X receptor

GLP-1Glucagonlike peptide 1

HDLHigh density lipoprotein

IBATIleal bile acid transporter

IBS-CConstipation-predominant irritable bowel syndrome

HDLHigh density lipoprotein

T2DMType2 diabetes mellitus

Mats Rudling, Michael Camilleri, Hans Graffner, Jens Juul Holst and Leif Rikner contributed equally to this work.

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Autor: Mats Rudling - Michael Camilleri - Hans Graffner - Jens Juul Holst - Leif Rikner

Fuente: https://link.springer.com/







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