Study of Liraglutide Versus Insulin on Liver Fat Fraction in Patients With Type 2 Diabetes (LIRAINS)

August 25, 2014 updated by: Centre hospitalier de l'Université de Montréal (CHUM)

Randomized Trial of Liraglutide and Insulin Therapy on Hepatic Steatosis as Measured by MRI and MRS in Metformin-treated Patients With Type 2 Diabetes: an Open Pilot Study

This study is conducted to test the hypothesis that in type 2 diabetic adults with fatty liver who are resistant to metformin, treatment with liraglutide in combination with metformin will cause an absolute reduction in liver fat superior to insulin-metformin treatment within a 3-month period, as measured by magnetic resonance imaging (MRI).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: Non-alcoholic fatty liver disease (NAFLD) can now be identified in 70% of patients with type 2 diabetes. Insulin can be introduced at any point in the treatment of diabetes, but is potentially lipogenic. Preliminary studies have shown conflicting results on the impact of insulin on fatty liver.

Objectives: This study is conducted to test the hypothesis that in type 2 diabetic adults with NAFLD who are resistant to metformin, treatment with liraglutide in combination with metformin will cause an absolute reduction in liver fat superior to insulin-metformin treatment within a 3-month period, as measured by in vivo MRI and MRS.

Design: This will be a prospective, open label, randomized parallel trial to evaluate whether 12 weeks of treatment with a) liraglutide-metformin will improve steatosis in type 2 diabetic adults with NAFLD compared to treatment with b) insulin-metformin. Before and post-treatment MRI and MRS will be read blindly for quantification of steatosis. The primary outcome measure is defined as an improvement in steatosis of 5% before and after treatment between the 2 treatment groups.

Methods: Thirty-six patients will be randomized to either study group. After baseline metabolic measurements by blood sampling, transient ultrasound elastography, MRI and MRS, all subjects will be given metformin with a starting dose of 500 mg in one tablet twice daily. In addition, patients will be randomized to receive either liraglutide (0.6 - 1.8 mg subcutaneous per day ) or insulin glargine with an initial bedtime starting dose of 10 IU for a duration of 3 months.

Expected results: The results of this study will provide preliminary data for a large scale study comparing the 2 therapeutic regimen and establish the utility of MRI and MRS to monitor medical treatment in diabetic patients with fatty liver disease.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montréal, Quebec, Canada, H2W 1T7
        • Centre Hospitalier de l'Universite de Montreal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Are 18 y.o. or older at screening (first visit),
  • Are ambulatory,
  • Are known for type 2 diabetes with criteria of failure of metformin monotherapy, metformin-sulfonylurea, metformin-repaglinide combined therapy defined as HbA1C ≥6.5,
  • Abdominal girth > 94 cm for men and > 80 cm for women,
  • Understand French or English instruction,
  • Able to comprehend and willingness to provide voluntary consent.

Exclusion Criteria:

  • Have any contra-indications for MRI (such as metallic implants, pacemaker or claustrophobia),
  • Have type 1 diabetes or have had episodes of ketoacidosis,
  • Have any major debilitating disease including malignant disorders,
  • Have had, within the last 6 months, evidence of significant heart disease or stroke, including myocardial infarction, unstable angina, coronary bypass and/or percutaneous transluminal coronary angioplasty (PTCA), congestive heart failure (New York Heart Association Class III-IV), or severe ischemic disease,
  • Patients having received insulin within 3 months prior to screening,
  • Have a serum creatine above >150 mmol/L or estimated GFR < 30 mL/min,
  • Women seeking pregnancy,
  • Have a history of chronic liver disease other than NAFLD, including HBV and HCV infection, hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, autoimmune hepatitis,
  • Current or previous use of oral or injectable corticosteroids,
  • Have excessive alcohol intake, defined as a daily limit of 30 g (3 drinks) for men and 20 g (2 drinks) for women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Liraglutide-Metformin

Liraglutide (Victoza, Novo Nordisk) at a dose of 0.6 - 1.8 mg subcutaneous per day until the end of the study.

All subjects will be given metformin with a starting dose of 500 mg in one tablet twice daily given before or during meals for the duration of the study.
Drug: Liraglutide-metformin vs insulin-metformin

Liraglutide (Victoza, Novo Nordisk) at a dose of 0.6 - 1.8 mg subcutaneous per day.

Insulin glargine (Lantus, Sanofi-Aventis) with an initial bedtime starting dose of 10 IU.

Other Names:
  • Lantus
  • Victoza
  • Liraglutide
  • Insulin glargine
EXPERIMENTAL: Insulin-Metformin

Insulin glargine (Lantus, Sanofi-Aventis) with an initial bedtime starting dose of 10 IU. The patients will be taught to increase their insulin dose by 1 unit each day until achieving an FPG ≤ 7.0 mmol/L.

All subjects will be given metformin with a starting dose of 500 mg in one tablet twice daily given before or during meals for the duration of the study.
Drug: Liraglutide-metformin vs insulin-metformin

Liraglutide (Victoza, Novo Nordisk) at a dose of 0.6 - 1.8 mg subcutaneous per day.

Insulin glargine (Lantus, Sanofi-Aventis) with an initial bedtime starting dose of 10 IU.

Other Names:
  • Lantus
  • Victoza
  • Liraglutide
  • Insulin glargine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To determine liver fat fraction evolution induced by liraglutide and insulin
Time Frame: 12 weeks
Improvement in liver steatosis defined by change in liver fat fraction as measured by MRI and MR spectroscopy at baseline and 12 weeks of treatment.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborators

Radiological Society of North America
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Diabetes Québec
Canadian Heads of Academic Radiology-GE Healthcare Development Award

Investigators

  • Principal Investigator: An Tang, MD, Centre de Recherche du Centre Hospitalier de l'Université de Montréal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (ACTUAL)

June 1, 2014

Study Completion (ACTUAL)

June 1, 2014

Study Registration Dates

First Submitted

July 20, 2011

First Submitted That Met QC Criteria

July 21, 2011

First Posted (ESTIMATE)

July 22, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

August 27, 2014

Last Update Submitted That Met QC Criteria

August 25, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CE09.159

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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