NCT02721888

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome and type 2 diabetes. NAFLD, in patients with type 2 diabetes, has been shown to be associated with lipid abnormalities (such as hypertriglyceridemia and decreased HDL-cholesterol) and increased cardiovascular risk. Such lipid abnormalities (hypertriglyceridemia and decreased HDL-cholesterol) are very frequent in patients with type 2 diabetes. Moreover, NAFLD is a risk for further development of cirrhosis (estimated between 3 and 5%). Animal studies have shown that liraglutide is able to decrease liver fat content, but the effect of liraglutide on liver fat content in patients with diabetes remains unknown. In addition, human studies with liraglutide have shown significant modification of plasma lipids, such as reduction of plasma triglycerides and LDL-cholesterol. However, the mechanisms responsible for these liraglutide induced lipid modifications are not yet known. Because increased in liver fat content and hypertriglyceridemia are associated in patients with type 2 diabetes, it seems interesting to study the effect of liraglutide on both liver fat content and lipid metabolism using gold-standard methods (proton-spectroscopy for liver fat content assessment and kinetic study with stable isotope to study lipoprotein metabolism). This is a monocentric study. Fatty liver content will be performed by proton-spectroscopy in patients with type 2 diabetes (n=120) before and after a 6 month period of liraglutide therapy (1.2 mg/day). Moreover, an in vivo kinetic study will be performed with stable isotopes (13C leucine) in 10 patients among the 120 patients with type 2 diabetes (n=10) before and after a 6-month period of liraglutide (1.2 mg/day) therapy. Each kinetic study will be performed during a 2-day hospitalization For the main study, 3 visits will be performed:

  • a first visit at T0, before starting the treatment with liraglutide, including clinical and biological measurements and liver fat content assessment by proton-spectroscopy
  • a visit at 3 months including clinical and biological measurements
  • and a visit at 6 months including clinical and biological measurements and liver fat content assessment by proton-spectroscopy For the kinetic substudy, performed in 10 patients, a kinetic study with stable isotope will been performs during a 48h-hospitalization before starting the treatment with liraglutide and after 6 month-treatment with liraglutide

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
127

participants targeted

Target at P50-P75 for phase_4 type-2-diabetes

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 10, 2012

Completed
3.6 years until next milestone

First Submitted

Initial submission to the registry

February 29, 2016

Completed
29 days until next milestone

First Posted

Study publicly available on registry

March 29, 2016

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 2, 2019

Completed
Last Updated

February 6, 2026

Status Verified

February 1, 2026

Enrollment Period

7.2 years

First QC Date

February 29, 2016

Last Update Submit

February 4, 2026

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (11)

  • Effect of liraglutide on fatty liver content evaluated by proton-spectroscopy (1H-spectroscopy and lipoprotein kinetics, in patients with type 2 diabetes

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Very Low Density Lipoprotein 1 (VLDL1) apolipoprotein B (apoB) production rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Very Low Density Lipoprotein 2 (VLDL2) apolipoprotein B (apoB) production rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Intermediate Density Lipoprotein (IDL) apolipoprotein B (apoB) production rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Low Density Lipoprotein (LDL) apolipoprotein B (apoB) production rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on High Density Lipoprotein (HDL) apolipoprotein A1 (apoA1) production rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Very Low Density Lipoprotein 1 (VLDL1) apolipoprotein B (apoB) fractional catabolic rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Very Low Density Lipoprotein 2 (VLDL2) apolipoprotein B (apoB) fractional catabolic rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Intermediate Density Lipoprotein (IDL) apolipoprotein B (apoB) fractional catabolic rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on Low Density Lipoprotein (LDL) apolipoprotein B (apoB) fractional catabolic rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Effects of liraglutide on High Density Lipoprotein (HDL) apolipoprotein A1 (apoA1) fractional catabolic rate

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

Secondary Outcomes (3)

  • Modification of body weight

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Modification of subcutaneous fat by Magnetic Resonance Imaging (MRI)

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

  • Modification of visceral fat by Magnetic Resonance Imaging (MRI)

    Before and after 6 month-treatment with liraglutide (1.2 mg/day)

Study Arms (1)

Main study

EXPERIMENTAL
Drug: LiraglutideDrug: MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy)Biological: Blood sampleOther: Kinetic substudy (10 patients)

Interventions

LiraglutideDRUG
Main study
Blood sampleBIOLOGICAL
Main study
MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy)DRUG
Main study
Kinetic substudy (10 patients)OTHER
Main study

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with type 2 diabetes
  • Patients treated by metformin and/or sulfonylureas (or glinides) and/or acarbose and/or insulin,
  • HbA1C \>= 7 %,
  • Patients who gave their written consent.
  • For the kinetic substudy:
  • Patients who have the typical features of diabetic dyslipidemia (triglycerides \>= 1.50 g/l and/or HDL\<0.50 g/l \[women\], 0.40 g/l \[men\])

You may not qualify if:

  • Treatment with thiazolidinediones or other Glucagon-like peptide-1(GLP1) agonist.
  • No treatment with a Dipeptidyl peptidase-4 (DPP4) inhibitor during the 3 previous months,
  • Renal or hepatic failure,
  • Contra-indication for proton-spectroscopy (pacemaker, implantable prosthesis,..),
  • Pregnancy.
  • For the kinetic substudy:
  • Patients on hypolipidemic agents

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CHU de Dijon

Dijon, 21079, France

Location

Related Publications (3)

  • Verges B, Duvillard L, Pais de Barros JP, Bouillet B, Baillot-Rudoni S, Rouland A, Sberna AL, Petit JM, Degrace P, Demizieux L. Liraglutide Reduces Postprandial Hyperlipidemia by Increasing ApoB48 (Apolipoprotein B48) Catabolism and by Reducing ApoB48 Production in Patients With Type 2 Diabetes Mellitus. Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2198-2206. doi: 10.1161/ATVBAHA.118.310990.

    PMID: 30026275RESULT

  • Denimal D, Bergas V, Pais-de-Barros JP, Simoneau I, Demizieux L, Passilly-Degrace P, Bouillet B, Petit JM, Rouland A, Bataille A, Duvillard L, Verges B. Liraglutide reduces plasma dihydroceramide levels in patients with type 2 diabetes. Cardiovasc Diabetol. 2023 May 4;22(1):104. doi: 10.1186/s12933-023-01845-0.

    PMID: 37143040DERIVED

  • Verges B, Duvillard L, Pais de Barros JP, Bouillet B, Baillot-Rudoni S, Rouland A, Petit JM, Degrace P, Demizieux L. Liraglutide Increases the Catabolism of Apolipoprotein B100-Containing Lipoproteins in Patients With Type 2 Diabetes and Reduces Proprotein Convertase Subtilisin/Kexin Type 9 Expression. Diabetes Care. 2021 Apr;44(4):1027-1037. doi: 10.2337/dc20-1843. Epub 2021 Feb 2.

    PMID: 33531418DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

LiraglutideMagnetic Resonance SpectroscopyBlood Specimen Collection

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1Glucagon-Like PeptidesProglucagonGastrointestinal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative TechniquesSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, Operative

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 29, 2016

First Posted

March 29, 2016

Study Start

July 10, 2012

Primary Completion

October 2, 2019

Last Updated

February 6, 2026

Record last verified: 2026-02

Locations

FR(1)