Clinical trial NCT02147925: Efficacy Study of Liraglutide vs.Sitagliptin vs. Glargine on Liver Fat in T2DM Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: Non-alcoholic fatty liver disease
Glucagon-like peptide-1 receptor agonists
Diabetes mellitus, type 2
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2014-05-28
Enrollment: 75
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Intrahepatic lipids (IHL)
timeFrame: 26-week
Secondary outcomes:
measure: Change of abdominal subcutaneous adipose tissue(SAT)
timeFrame: 26 weeks
measure: Change of visceral adipose tissue(VAT)
timeFrame: 26 weeks
measure: Change in hemoglobin A1c(HbA1c)
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Jianping Weng, Doctor
role: STUDY_DIRECTOR
References: