Antidiabetic Effects on Intrahepatic Fat

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Non-Alcoholic Fatty Liver Disease, Type2 Diabetes

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Metformin
* Drug: Gliclazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-70 years; Type 2 diabetes mellitus; Not used antidiabetic drugs within 3 months; HbA1c(7-10%); Presence of fatty liver disease (hepatic fat content ≥ 20% by quantitative ultrasonography); Female subjects：post-menopausal women, take contraceptive measures three months before the test screening and can persist throughout the experimental period; Body mass index (BMI) 20-35kg/m2, and stable Weight 3 months(less than 10% volatility); patients signed the informed consent. Exclusion Criteria: Used antidiabetic drugs or any other possible hepatic steatosis associated with drugs within the past three months; Suffering from pancreatitis or other pancreatic diseases or have other similar history; GLP-1 analogs or sulfonylurea allergy history; Liver dysfunction (aspartate aminotransferase ≥ 2.5 times of the normalupper limit); Moderate to severe renal insufficiency (eGFR<60ml/min/1.73m2,calculated according to MDRD); Female subjects drinking> 14 units / week; male subjects drinking> 21 units/week; A history of metabolic or autoimmune liver diseases or viral hepatitis diseases; A history of medullary thyroid carcinoma, multiple endocrine neoplasia 2 or family history; Congestive heart failure (NYHA grade Ⅲ - Ⅳ grade); Severe gastrointestinal diseases; Other serious concomitant diseases; Pregnant or planning pregnancy; The researchers believe that the subjects with proliferative retinopathy or macular degeneration need urgentl treatment; 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.

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 80 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>the dosage of liraglutide 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 | Drug: Liraglutide<br>* the dosage of liraglutide 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<br>* Other names: Victoza,Novo Nordisk;|
| Active Comparator: Metformin<br>the dosage of merformin 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 | Drug: Metformin<br>* the dosage of metformin 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<br>* Other names: Glucophage,Bristol-Myers Squibb;|
| Active Comparator: Gliclazide<br>the initial dosage of gliclazide 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 | Drug: Gliclazide<br>* the initial dosage of gliclazide 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<br>* Other names: Diamicron MR,Servier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intrahepatic fat | intrahepatic fat change from baseline by quantitative ultrasound | -7±3days; 168±3days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver function | serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) | -7±3days; 28±3days; 84±3days; 168±3days | 
| Lipid | total cholesterol (CH), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) | -7±3days; 28±3days; 84±3days; 168±3days | 
| Plasma glucose in standard meal tolerance test | plasma glucose was measured at 0, 30, 60, and 120 min after ingestion of the meal | -7±3days; 168±3days | 
| Plasma insulin in standard meal tolerance test | plasma insulin was measured at 0, 30, 60, and 120 min after ingestion of the meal | -7±3days; 168±3days | 
| Glucose control | fasting blood glucose (FBG), postprandial blood glucose (PBG) | 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days | 
| HbA1c | glycosylated hemoglobin A 1c (HbA1c) was measured by high-performance liquid chromatography | -7±3days; 84±3days; 168±3days | 
| Body composition | fat mass and lean tissue were measured by dual-energy X-ray absorptiometry | -7±3days; 168±3days | 
| Weight | body weight | 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days | 
| WC | waist circumference | 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3days; 168±3days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liraglutide, Metformin, Gliclazide