Efficacy Study of Liraglutide vs.Sitagliptin vs. Glargine on Liver Fat in T2DM Subjects

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Liraglutide combined with metformin
* Drug: Insulin glargine combined with metformin
* Drug: Sitagliptin combined with metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liraglutide<br>Liraglutide combined with metformin | Drug: Liraglutide combined with metformin<br>* 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<br>* Other names: Victoza®, Novo Nordisk;|
| Active Comparator: Insulin glargine<br>Insulin glargine combined with metformin | Drug: Insulin glargine combined with metformin<br>* The initial dose will be 0.2 unit/kg/d<br>* Other names: Lantus®, Sanofi;|
| Active Comparator: Sitagliptin<br>Sitagliptin combined with metformin | Drug: Sitagliptin combined with metformin<br>* The dose throughout the study will be 100mg per day.<br>* Other names: Januvia®, Merck & Co. Inc.;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic fatty liver disease, Glucagon-like peptide-1 receptor agonists, Diabetes mellitus, type 2