Antidiabetic Effects on Intrahepatic Fat

Sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Other)

Overall Status

Completed

CT.gov ID

NCT03068065

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

5.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease Type2 Diabetes	Drug: Liraglutide Drug: Metformin Drug: Gliclazide	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

87 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Liraglutide 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 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 Other Names: Victoza,Novo Nordisk
Active Comparator: Metformin 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 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 Other Names: Glucophage,Bristol-Myers Squibb
Active Comparator: Gliclazide 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 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 Other Names: Diamicron MR,Servier

Arm

Intervention/Treatment

Active Comparator: Liraglutide

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

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

Other Names:

Victoza,Novo Nordisk

Active Comparator: Metformin

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

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

Other Names:

Glucophage,Bristol-Myers Squibb

Active Comparator: Gliclazide

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

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

Other Names:

Diamicron MR,Servier

Outcome Measures

Primary Outcome Measures

Intrahepatic fat [-7±3days; 168±3days]
intrahepatic fat change from baseline by quantitative ultrasound

Secondary Outcome Measures

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

Other Outcome Measures

Number of Participants with gliclazide, liraglutide or metformin adverse events as a measure of safety and tolerability [-7±3days; 0±3days; 14±3days; 28±3days; 56±3days; 84±3days; 112±3days; 140±3day;168±3days]
adverse events caused by the drugs

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.