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

Armstrong MJ, Hull D, Guo K, Barton D, Hazlehurst JM, Gathercole LL, Nasiri M, Yu J, Gough SC, Newsome PN, Tomlinson JW

Journal of hepatology21 Sept 2015Cited by 354 (Europe PMC)

PMID26394161PMCIDPMC4713865DOI10.1016/j.jhep.2015.08.038PepBankPUB-26394161

Summary

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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

11 results from studies that gave the peptide. 11 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with biopsy-proven NASH, 12 weeks of liraglutide reduced BMI compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered body mass index more than placebo over 12 weeks.
Peptide
Liraglutide
Outcome
DecreaseBMI change
Study
n = 14
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Measurements
BMI change
−1.9 kg/m(2)
liraglutide
BMI change
0.04 kg/m(2)
placebo
Source sentences
Summary
Liraglutide reduced BMI (-1.9 vs. +0.04kg/m(2); p<0.001)
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416101
02HumanRandomized controlled trialEfficacy outcome
In adults with biopsy-proven NASH, liraglutide lowered HbA1c compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered HbA1c (long-term blood sugar) more than placebo over 12 weeks.
Peptide
Liraglutide
Outcome
DecreaseHbA1c change
Study
n = 14
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Measurements
HbA1c change
−0.3%
liraglutide
HbA1c change
0.3%
placebo
Source sentences
Summary
HbA1c (-0.3 vs. +0.3%; p<0.01)
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416102
03HumanRandomized controlled trialEfficacy outcome
In adults with biopsy-proven NASH, liraglutide lowered LDL cholesterol compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered LDL cholesterol more than placebo over 12 weeks.
Peptide
Liraglutide
Outcome
DecreaseLDL cholesterol change
Study
n = 14
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Measurements
LDL cholesterol change
−0.7 mmol/L
liraglutide
LDL cholesterol change
0.05 mmol/L
placebo
Source sentences
Summary
cholesterol-LDL (-0.7 vs. +0.05mmol/L; p<0.01)
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416103
04HumanRandomized controlled trialEfficacy outcome
In adults with biopsy-proven NASH, liraglutide lowered ALT compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered the liver enzyme ALT more than placebo over 12 weeks.
Peptide
Liraglutide
Outcome
DecreaseALT change
Study
n = 14
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Measurements
ALT change
−54 IU/L
liraglutide
ALT change
−4 IU/L
placebo
Source sentences
Summary
ALT (-54 vs. -4.0IU/L; p<0.01)
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416104
05HumanRandomized controlled trialMechanism
In adults with biopsy-proven NASH, liraglutide reduced serum leptin compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered blood leptin more than placebo over 12 weeks.
Peptide
Liraglutide
Outcome
DecreaseSerum leptin
Study
n = 14
Comparator
Placebo
Outcome group
Inflammation markers · Metabolic and weight
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Source sentences
Summary
serum leptin, adiponectin, and CCL-2 (all p<0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416105
06HumanRandomized controlled trialMechanism
In adults with biopsy-proven NASH, liraglutide reduced serum adiponectin compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered blood adiponectin more than placebo over 12 weeks.
Peptide
Liraglutide
Outcome
DecreaseSerum adiponectin
Study
n = 14
Comparator
Placebo
Outcome group
Inflammation markers · Metabolic and weight
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Source sentences
Summary
serum leptin, adiponectin, and CCL-2 (all p<0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416106
07HumanRandomized controlled trialMechanism
In adults with biopsy-proven NASH, liraglutide reduced serum CCL-2 compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered blood CCL-2, an inflammation signal, more than placebo over 12 weeks.
Peptide
Liraglutide
Outcome
DecreaseSerum CCL-2
Study
n = 14
Comparator
Placebo
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Source sentences
Summary
serum leptin, adiponectin, and CCL-2 (all p<0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416107
08HumanRandomized controlled trialMechanism
In adults with biopsy-proven NASH, liraglutide increased hepatic insulin sensitivity compared with placebo.
In plain wordsIn adults with NASH, liraglutide improved how well the liver responds to insulin compared with placebo.
Peptide
Liraglutide
Outcome
IncreaseHepatic insulin sensitivity (suppression of hepatic endogenous glucose production)
Study
n = 14
Comparator
Placebo
Outcome group
Glycemic control · Liver
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Source sentences
Summary
Liraglutide increased hepatic insulin sensitivity (-9.36 vs. -2.54% suppression of hepatic endogenous glucose production with low-dose insulin; p<0.05).
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416108
09HumanRandomized controlled trialMechanism
In adults with biopsy-proven NASH, liraglutide increased adipose tissue insulin sensitivity globally, shown by better insulin suppression of lipolysis than placebo.
In plain wordsIn adults with NASH, liraglutide improved how well fat tissue responds to insulin compared with placebo.
Peptide
Liraglutide
Outcome
IncreaseGlobal adipose tissue insulin sensitivity (suppression of lipolysis)
Study
n = 14
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Source sentences
Summary
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)
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416109
10HumanRandomized controlled trialMechanism
In adults with biopsy-proven NASH, liraglutide increased insulin sensitivity within subcutaneous adipose tissue compared with placebo.
In plain wordsIn adults with NASH, liraglutide improved how well under-the-skin fat responds to insulin compared with placebo.
Peptide
Liraglutide
Outcome
IncreaseSubcutaneous adipose tissue insulin sensitivity (suppression of lipolysis)
Study
n = 14
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Source sentences
Summary
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).
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416110
11HumanRandomized controlled trialMechanism
In adults with biopsy-proven NASH, liraglutide decreased hepatic de novo lipogenesis in vivo compared with placebo.
In plain wordsIn adults with NASH, liraglutide lowered fat production in the liver compared with placebo.
Peptide
Liraglutide
Outcome
DecreaseHepatic de novo lipogenesis in vivo
Study
n = 14
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
1.8 mg · 12 weeksAs given in this study (human).
Measurements
Hepatic de novo lipogenesis change
−1.26%
liraglutide
Hepatic de novo lipogenesis change
1.3%
placebo
Source sentences
Summary
liraglutide decreased hepatic de novo lipogenesis in vivo (-1.26 vs. +1.30%; p<0.05)
1 context sentence(design, population, supporting numbers)
Summary · context
Fourteen 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).
Show in the study text Report a problemFND-2639416111

Studies that did not test the peptide alone1

In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Liraglutide.

12LabNot a test of Liraglutide aloneIn vitro (cells)Mechanism
In primary human hepatocytes, a GLP-1 receptor agonist decreased lipogenesis by 24.6% compared with untreated controls.
In plain wordsIn cells, a GLP-1 receptor agonist lowered fat production in human liver cells compared with untreated cells.
Peptide
Liraglutide
Outcome
DecreaseLipogenesis in primary human hepatocytes
Study
humann: not reported in source
Primary human hepatocytes
Comparator
Untreated controls
Outcome group
Liver fat and liver function · Liver
Measurements
Lipogenesis decrease
24.6%
primary human hepatocytes
Source sentences
Summary
the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p<0.01).
1 context sentence(design, population, supporting numbers)
Summary · context
In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Show in the study text Report a problemFND-2639416112

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT01237119

Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis

University of Birminghamn = 52Aug 2010 to Jul 2014

Nonalcoholic Steatohepatitis

Trial page ClinicalTrials.govUpdated 23 Mar 2016

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

PepBank is a research reference. Talk to a doctor before you use any peptide.

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

Summary

Results from this study12

Studies that did not test the peptide alone1

Registered trials1

Liraglutide Efficacy and Action in Non-Alcoholic Steatohepatitis

Version history

Subjects

Publication types

MeSH terms

Keywords