Effect of Liraglutide on Fatty Liver Content and Lipoprotein Metabolism

Phase 4

Terminated

• Conditions: Type 2 Diabetes
• Interventions: Drug: Liraglutide; Drug: MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy); Biological: Blood sample; Other: Kinetic substudy (10 patients)

• Registration Number: NCT02721888
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

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

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07-10
• Study First Submitted: 2016-02-29
• Study First Submitted QC: 2016-03-23
• Study First Posted: 2016-03-29
• Primary Completion: 2019-10-02
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 127

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Main study	Kinetic substudy (10 patients)	-
Main study	Blood sample	-
Main study	MRI/ MRS (Magnetic Resonance Imaging /Magnetic Resonance Spectroscopy)	-
Main study	Liraglutide	-

Primary Outcome Measures

Name	Time	Method
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 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 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 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 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 High Density Lipoprotein (HDL) apolipoprotein A1 (apoA1) 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)

Secondary Outcome Measures

Name	Time	Method
Modification of visceral fat by Magnetic Resonance Imaging (MRI)	Before and after 6 month-treatment with liraglutide (1.2 mg/day)	Modification of visceral fat by MRI induced by liraglutide 1.2mg/d therapy
Modification of body weight	Before and after 6 month-treatment with liraglutide (1.2 mg/day)	Modification of weight, induced by liraglutide 1.2 mg/d therapy.
Modification of subcutaneous fat by Magnetic Resonance Imaging (MRI)	Before and after 6 month-treatment with liraglutide (1.2 mg/day)	Modification of subcutaneous fat by MRI induced by liraglutide 1.2mg/d therapy

Trial Locations

Locations (1)

CHU de Dijon; 🇫🇷 Dijon, France