Evidence map›Paper›PMID 34535644›Full record

Trial reportNature communications2021

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

Stephen A Harrison, Nadege Gunn, Guy W Neff, Anita Kohli, Liping Liu, Abbey Flyer, Lawrence Goldkind, Adrian M Di Bisceglie

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 71 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 8 pooled it
12.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03656744 phase2completednot on this map

A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adults With NASH and T2DM

TypeinterventionalSponsorHighTide Therapeutics (Hong Kong) LimitedRan2018 to 2020Enrolled101ConditionsFatty Liver, Nonalcoholic, NAFLD, Nonalcoholic Fatty Liver Disease, Nonalcoholic SteatohepatitisArmsHTD1801, Placebo
NCT05647915 phase4completednot on this mapstarted 2023, after this paper: background citation

Assess the Effects of Berberine in Reducing Abdominal Visceral Adipose Tissue Among Individuals with Obesity and Non-alcoholic Fatty Liver Disease

TypeinterventionalSponsorChina National Center for Cardiovascular DiseasesRan2023 to 2024Enrolled337ConditionsObesity, Obesity, Abdominal, NAFLDArmsBerberine plus lifestyle intervention, Placebo plus lifestyle intervention
3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 8 syntheses or guidelines pooled it, 113 citations in OpenAlex.

  1. Pooled it
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  3. Berberine and health outcomes: an overview of systematic reviews.BMC complementary medicine and therapies · 2025
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  20. Current management of MASLD in type 2 diabetes.Hormones (Athens, Greece) · 2026
    Review

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Stephen A HarrisonPinnacle Clinical Research, San Antonio, TX, USA. stephenharrison87@gmail.com.
Nadege GunnPinnacle Clinical Research, Austin, TX, USA.
Guy W NeffCovenant Research, Sarasota, FL, USA.
Anita KohliArizona Liver Health, Chandler, AZ, USA.
Liping LiuHightide Therapeutics, Rockville, MD, USA.
Abbey FlyerPacific Northwest Statistical Consulting, Woodlinville, WA, USA.
Lawrence GoldkindUniformed Services University of Health Sciences, Bethesda, MA, USA.
Adrian M Di BisceglieHightide Therapeutics, Rockville, MD, USA.ORCID 0000-0002-6075-9305
Pinnacle Clinical Research · USArizona Liver Health · USCovenant Research and Clinics (United States) · USUniformed Services University of the Health Sciences · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

Proof of Concept StudyAdiposityAdultAgedBerberineDiabetes Mellitus, Type 2FemaleGlycated HemoglobinHumansLiverMaleMiddle AgedNon-alcoholic Fatty Liver DiseaseBerberineGlycated Hemoglobin

Identifiers

PMID34535644
PMCPMC8448729
OpenAlexW3201436860

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.