Effect of Liraglutide on Fatty Liver Content and Lipoprotein Metabolism

NCT ID: NCT02721888

Last Updated: 2024-02-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-10

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

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Main study

Group Type: EXPERIMENTAL

Liraglutide

Intervention Type: DRUG

MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy)

Intervention Type: DRUG

Blood sample

Intervention Type: BIOLOGICAL

Kinetic substudy (10 patients)

Intervention Type: OTHER

Interventions

Liraglutide

Intervention Type: DRUG

MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy)

Intervention Type: DRUG

Blood sample

Intervention Type: BIOLOGICAL

Kinetic substudy (10 patients)

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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])

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU de Dijon

Dijon, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 37143040 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33531418 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30026275 (View on PubMed)

Other Identifiers

VERGES NOVO 2012

Identifier Type: -

Identifier Source: org_study_id