Evidence map›Paper›PMID 26394161›Full record

Trial reportJournal of hepatology2016

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis.

Matthew J Armstrong, Diana Hull, Kathy Guo, Darren Barton, Jonathan M Hazlehurst, Laura L Gathercole, Maryam Nasiri, Jinglei Yu, Stephen C Gough, Philip N Newsome and 1 more

Registry-linked trialOpen access · hybridFull text readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01237119 (48-week Phase II, Randomised, Double Blinded Placebo Controlled Multicentre Trial on Liraglutide's Safety, Efficacy and Action on Liver Histology and Metabolism in Overweight Patients With NASH +/- Type II Diabetes), which is not on this map. Cited by 219 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
219citing papers in PubMed, 12 pooled it
20.7field-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.

NCT01237119 phase2completednot on this map

48-week Phase II, Randomised, Double Blinded Placebo Controlled Multicentre Trial on Liraglutide's Safety, Efficacy and Action on Liver Histology and Metabolism in Overweight Patients With NASH +/- Type II Diabetes

TypeinterventionalSponsorUniversity of BirminghamRan2010 to 2014Enrolled52ConditionsNonalcoholic SteatohepatitisArmsLiraglutide, Liraglutide-placebo
3 · Its place in the literature

Who cites it

219 citing papers in PubMed, 12 syntheses or guidelines pooled it, 426 citations in OpenAlex.

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  8. GLP-1a: Going beyond Traditional Use.International journal of molecular sciences · 2022
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159 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Matthew J ArmstrongNIHR Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK. Electronic address: mattyarm2010@googlemail.com.
Diana HullNIHR Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK.
Kathy GuoNIHR Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK.
Darren BartonCRUK Clinical Trials Unit, University of Birmingham, Birmingham, UK.
Jonathan M HazlehurstCentre for Endocrinology, Diabetes and Metabolism, Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, UK.
Laura L GathercoleCentre for Endocrinology, Diabetes and Metabolism, Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, UK.
Maryam NasiriCentre for Endocrinology, Diabetes and Metabolism, Institute of Biomedical Research, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, UK.
Jinglei YuSchool of Sport, Exercise & Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
Stephen C GoughOxford Centre for Diabetes, Endocrinology and Metabolism, and NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK.
Philip N NewsomeNIHR Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK.
Jeremy W TomlinsonOxford Centre for Diabetes, Endocrinology and Metabolism, and NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK. Electronic address: jeremy.tomlinson@ocdem.ox.ac.uk.
University of Birmingham · GBNIHR Birmingham Liver Biomedical Research Unit · GBOxford Centre for Diabetes, Endocrinology and Metabolism · GBUniversity of Oxford · GB

Funding

Medical Research Council G0802765Medical Research Council MR/L022699/1Wellcome TrustWellcome Trust 089780/Z/09/Z
6 · The paper itself

Abstract

BACKGROUND &

aimsInsulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.

methodsFourteen patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomised, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.

resultsLiraglutide reduced BMI (-1.9 vs. +0.04kg/m(2); p<0.001), HbA1c (-0.3 vs. +0.3%; p<0.01), cholesterol-LDL (-0.7 vs. +0.05mmol/L; p<0.01), ALT (-54 vs. -4.0IU/L; p<0.01) and serum leptin, adiponectin, and CCL-2 (all p<0.05). Liraglutide increased hepatic insulin sensitivity (-9.36 vs. -2.54% suppression of hepatic endogenous glucose production with low-dose insulin; p<0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (-24.9 vs. +54.8pmol/L insulin required to ½ maximally suppress serum non-esterified fatty acids; p<0.05), and specifically within subcutaneous adipose tissue (p<0.05). In addition, liraglutide decreased hepatic de novo lipogenesis in vivo (-1.26 vs. +1.30%; p<0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p<0.01).

conclusionsLiraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH.

Indexed as

LiraglutideNon-alcoholic Fatty Liver DiseaseAdultAgedBody Mass IndexDouble-Blind MethodDrug MonitoringFemaleGlucagon-Like Peptide 1Glucose Clamp TechniqueGlycated HemoglobinHumansHypoglycemic AgentsInsulin ResistanceLipid MetabolismLiverGlucagon-Like Peptide 1Glycated HemoglobinHypoglycemic AgentsLiraglutideAdipose tissueGlucagon-like peptide 1Insulin sensitivityLipolysisNon-alcoholic fatty liver

Identifiers

PMID26394161
PMCPMC4713865
OpenAlexW1758829516

What OpenQuestion holds

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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 OpenQuestion graph.