Clinical trial NCT03068065: Antidiabetic Effects on Intrahepatic Fat
Official title: Comparison of Efficacy of Liraglutide, Metformin and Gliclazide MR on Hepatic Lipid Content in Patients With Type 2 Diabetes (T2DM) and Non-alcoholic Fatty Liver (NAFLD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non-Alcoholic Fatty Liver Disease
Type2 Diabetes
Keywords: Liraglutide
Metformin
Gliclazide
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2017-03-01
Enrollment: 87
Sex: ALL
Minimum age (years): 17
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a 24-week single-center, open-label, parallel controlled group comparing gliclazide, liraglutide, and metformin effects on diabetes with nonalcoholic fatty liver disease.

Detailed description: Following enrollment, eligible participants were randomized (1:1:1) using computer-generated random numbers to the metformin (Glucophage, Bristol-Myers Squibb), liraglutide (Victoza, Novo Nordisk), or gliclazide (Diamicron, Servier) groups. All patients were informed about a proper diet and exercise. For the metformin group (n = 31), the dosage was 250 mg thrice a day during the first week, 500 mg thrice a day during the second week, and 1000 mg twice a day from the third week to the conclusion of the study. For the gliclazide group (n = 31), the initial dosage was 30 mg before breakfast, which was gradually titrated to a maximum of 120 mg/day to achieve a fasting capillary plasma glucose of \<7.0 mmol/L. For the liraglutide group (n = 31), the dosage was 0.6 mg/day during the first week, 1.2 mg/day during the second week, and 1.8 mg/day from the third week to the conclusion of the study.At the end of the study, data will be collected and analyzed.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-70 years;
2. Type 2 diabetes mellitus;
3. Not used antidiabetic drugs within 3 months;
4. HbA1c(7-10%);
5. Presence of fatty liver disease (hepatic fat content ≥ 20% by quantitative ultrasonography);
6. Female subjects：post-menopausal women, take contraceptive measures three months before the test screening and can persist throughout the experimental period;
7. Body mass index (BMI) 20-35kg/m2, and stable Weight 3 months(less than 10% volatility);
8. patients signed the informed consent.

Exclusion Criteria:

1. Used antidiabetic drugs or any other possible hepatic steatosis associated with drugs within the past three months;
2. Suffering from pancreatitis or other pancreatic diseases or have other similar history;
3. GLP-1 analogs or sulfonylurea allergy history;
4. Liver dysfunction (aspartate aminotransferase ≥ 2.5 times of the normalupper limit);
5. Moderate to severe renal insufficiency (eGFR\<60ml/min/1.73m2,calculated according to MDRD);
6. Female subjects drinking\> 14 units / week; male subjects drinking\> 21 units/week;
7. A history of metabolic or autoimmune liver diseases or viral hepatitis diseases;
8. A history of medullary thyroid carcinoma, multiple endocrine neoplasia 2 or family history;
9. Congestive heart failure (NYHA grade Ⅲ - Ⅳ grade);
10. Severe gastrointestinal diseases;
11. Other serious concomitant diseases;
12. Pregnant or planning pregnancy;
13. The researchers believe that the subjects with proliferative retinopathy or macular degeneration need urgentl treatment;
14. Subjects are using unknown ingredients or non herbal medicine preparations or local medicine, researchers believe that during the test the dose of traditional Chinese medicines can not be adjusted or disabled.

Primary outcomes:
measure: Intrahepatic fat
timeFrame: -7±3days; 168±3days
Secondary outcomes:
measure: Liver function
timeFrame: -7±3days; 28±3days; 84±3days; 168±3days
measure: Lipid
timeFrame: -7±3days; 28±3days; 84±3days; 168±3days
measure: Plasma glucose in standard meal tolerance test
timeFrame: -7±3days; 168±3days
measure: Plasma insulin in standard meal tolerance test
timeFrame: -7±3days; 168±3days
measure: Glucose control
timeFrame: 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days
measure: HbA1c
timeFrame: -7±3days; 84±3days; 168±3days
measure: Body composition
timeFrame: -7±3days; 168±3days
measure: Weight
timeFrame: 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days
measure: WC
timeFrame: 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days
Other outcomes:
measure: Number of Participants with gliclazide, liraglutide or metformin adverse events as a measure of safety and tolerability
timeFrame: -7±3days; 0±3days; 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3day;168±3days
Locations:
city: Nanjing
country: China
facility: at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
state: Jiangsu
Study officials:
affiliation: the Affiliated Drum Tower Hospital of Nanjing University
name: Dalong Zhu, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: