Efficacy Study of Liraglutide vs.Sitagliptin vs. Glargine on Liver Fat in T2DM Subjects (LIGHT-ON)

Efficacy of Liraglutide vs. Sitagliptin vs. Insulin Glargine Per Day on Liver Fat When Combined With Metformin in T2DM Subjects With Non-alcoholic Fatty-liver Disease

The aim of this study is to explore the effectiveness of liraglutide combined with metformin in non-alcoholic fatty-liver disease patients with type 2 diabetes mellitus (T2DM) compared to sitagliptin and insulin glargine in combination with metformin.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Liraglutide combined with metformin; Drug: Insulin glargine combined with metformin; Drug: Sitagliptin combined with metformin

Detailed Description

This is a 26-week, randomized, open-label, active controlled, parallel group, multi-centre trial.To compare the change of intrahepatic lipids (IHL) as measured by magnetic resonance spectroscopy(MRS) or MRI estimated proton density fat fraction (MRI-PDFF) as measured by MRI IDEAL IQ (Iterative Decomposition of water andfat with Echo Asymmetryand Least-squares estimation) in type 2 diabetic patients with non-alcoholic fatty-liver disease after a 26-week treatment of liraglutide, sitagliptin or insulin glargine per day combined with metformin.The primary endpoint will be defined by intrahepatic lipids (IHL) as measured by magnetic resonance spectroscopy (MRS) or MRI-PDFF as measured by MRI IDEAL IQ.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recorded Type 2 diabetes diagnosed at least 3 months before the study; At least 3 months treatment on a stable dose（≧1500mg/d）of metformin before the study
• 6.5%<HbA1c ≤10%
• Clinically diagnosed simple liver steatosis
• 30-75 years old
• Female subjects should be postmenopausal, surgically sterile, or using contraceptives for 3 months before screening and continuing throughout the study;
• BMI 20~35 kg/m2 and with a history of stable body weight (≤10%variation for ≥3 months)
• intrahepatic lipids (IHL) >10%

Exclusion Criteria:

• Type 1 diabetes
• Treatment within the last 3 months with Thiazolidinediones(TZDs), orlistat, insulin, any history of incretin based therapy or any other drugs associated with hepatic steatosis (including but not limited to glucocorticoids, tamoxifen, amiodarone or methotrexate)
• History or current episode of pancreatitis or other disease of the pancrea; Impaired liver function, defined as plasma alanine transaminase(ALT) >2.5 times of upper normal limit
• Moderate and severe renal insufficiency defined as MDRD formula glomerular filtration rate<60ml/min/1.73m2
• Weekly alcohol intake>14 units for women or >21 units for men
• Any history of liver disease including metabolic or auto-immune liver diseases or viral hepatitis
• History or family history of medullary thyroid cancer(MTC), or multiple endocrine neoplasia type 2(MEN-2)
• Congestive heart failure(NYHA III~IV)
• Severe gastric-intestinal diseases
• Pregnancy and/or intention of becoming pregnant
• Known proliferative retinopathy or maculopathy requiring acute treatment as judged by the Investigator; Use of non-herbal Chinese medicine or other non-herbal local medicine with unknown/unspecified content. Herbal traditional Chinese medicine or other local herbal medicines may, at the Investigator's discretion, be continued throughout the trial at an unchanged dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liraglutide; Liraglutide combined with metformin	Drug: Liraglutide combined with metformin; Liraglutide, 0.6mg per day for the first week, and will be increased to 1.2mg per day for the second week, and finally 1.8mg per day since the third week; Other Names: Victoza®, Novo Nordisk
Active Comparator: Insulin glargine; Insulin glargine combined with metformin	Drug: Insulin glargine combined with metformin; The initial dose will be 0.2 unit/kg/d; Other Names: Lantus®, Sanofi
Active Comparator: Sitagliptin; Sitagliptin combined with metformin	Drug: Sitagliptin combined with metformin; The dose throughout the study will be 100mg per day.; Other Names: Januvia®, Merck & Co. Inc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrahepatic lipids (IHL)	To compare the change of intrahepatic lipids (IHL) in type 2 diabetic patients with non-alcoholic fatty-liver disease after a 26-week treatment of liraglutide, sitagliptin or insulin glargine per day combined with metformin.	26-week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of abdominal subcutaneous adipose tissue(SAT)	To compare the change of SAT in type 2 diabetic patients	26 weeks
Change of visceral adipose tissue(VAT)	To compare the change of VAT in type 2 diabetic patients	26 weeks
Change in hemoglobin A1c(HbA1c)	To compare the change of HbA1c in type 2 diabetic patients	26 weeks

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Director: Jianping Weng, Doctor, Third Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: May 16, 2014
• First Submitted That Met QC Criteria: May 27, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): May 18, 2018
• Last Update Submitted That Met QC Criteria: May 17, 2018
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Non-alcoholic fatty liver disease; Diabetes mellitus, type 2; Glucagon-like peptide-1 receptor agonists
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Liraglutide; Metformin; Insulin Glargine; Sitagliptin Phosphate
• Other Study ID Numbers: IIS201404