Non-alcoholic Fatty Liver Disease
Conditions
Keywords
Non-alcoholic fatty liver disease, Glucagon-like peptide-1 receptor agonists, Diabetes mellitus, type 2
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.
Interventions
DRUGLiraglutide 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
DRUGInsulin glargine combined with metformin
The initial dose will be 0.2 unit/kg/d
DRUGSitagliptin combined with metformin
The dose throughout the study will be 100mg per day.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intrahepatic lipids (IHL) | 26-week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of abdominal subcutaneous adipose tissue(SAT) | 26 weeks | To compare the change of SAT in type 2 diabetic patients |
| Change of visceral adipose tissue(VAT) | 26 weeks | To compare the change of VAT in type 2 diabetic patients |
| Change in hemoglobin A1c(HbA1c) | 26 weeks | To compare the change of HbA1c in type 2 diabetic patients |
Countries
China
Outcome results
None listed