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A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes

Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt...

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Autores principales: Harrison, Stephen A., Gunn, Nadege, Neff, Guy W., Kohli, Anita, Liu, Liping, Flyer, Abbey, Goldkind, Lawrence, Di Bisceglie, Adrian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448729/
https://www.ncbi.nlm.nih.gov/pubmed/34535644
http://dx.doi.org/10.1038/s41467-021-25701-5
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author Harrison, Stephen A.
Gunn, Nadege
Neff, Guy W.
Kohli, Anita
Liu, Liping
Flyer, Abbey
Goldkind, Lawrence
Di Bisceglie, Adrian M.
author_facet Harrison, Stephen A.
Gunn, Nadege
Neff, Guy W.
Kohli, Anita
Liu, Liping
Flyer, Abbey
Goldkind, Lawrence
Di Bisceglie, Adrian M.
author_sort Harrison, Stephen A.
collection PubMed
description Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease −4.8% vs. −2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes.
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spelling pubmed-84487292021-10-04 A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes Harrison, Stephen A. Gunn, Nadege Neff, Guy W. Kohli, Anita Liu, Liping Flyer, Abbey Goldkind, Lawrence Di Bisceglie, Adrian M. Nat Commun Article Non-alcoholic steatohepatitis is frequently associated with diabetes and may cause progressive liver disease. Current treatment options are limited. Here we report on a prospective, randomised, double-blind, placebo-controlled trial of two doses of HTD1801 (berberine ursodeoxycholate, an ionic salt of berberine and ursodeoxycholic acid), versus placebo that was conducted in 100 subjects with fatty liver disease and diabetes (NCT03656744). Treatment was for 18 weeks with a primary endpoint of reduction in liver fat content measured by magnetic resonance imaging proton density fat fraction. Key secondary endpoints included improvement in glycemic control, liver-associated enzymes and safety. The pre-specified primary endpoint was met. Thus, subjects receiving 1000 mg twice a day of berberine ursodeoxycholate had significantly greater reduction in liver fat content than in placebo recipients (mean absolute decrease −4.8% vs. −2.0% (p = 0.011). Compared to placebo, subjects receiving this dose also experienced significant improvement in glycemic control as well as reductions in liver-associated enzymes and significant weight loss. Diarrhea and abdominal discomfort were the most frequently reported adverse events. We conclude that berberine ursodeoxycholate has a broad spectrum of metabolic activity in patients with presumed NASH and diabetes. It is relatively well tolerated and merits further development as a treatment for NASH with diabetes. Nature Publishing Group UK 2021-09-17 /pmc/articles/PMC8448729/ /pubmed/34535644 http://dx.doi.org/10.1038/s41467-021-25701-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Harrison, Stephen A.
Gunn, Nadege
Neff, Guy W.
Kohli, Anita
Liu, Liping
Flyer, Abbey
Goldkind, Lawrence
Di Bisceglie, Adrian M.
A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
title A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
title_full A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
title_fullStr A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
title_full_unstemmed A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
title_short A phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
title_sort phase 2, proof of concept, randomised controlled trial of berberine ursodeoxycholate in patients with presumed non-alcoholic steatohepatitis and type 2 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448729/
https://www.ncbi.nlm.nih.gov/pubmed/34535644
http://dx.doi.org/10.1038/s41467-021-25701-5
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