Antidiabetic Effects on Intrahepatic Fat

Phase 4

Completed

• Conditions: Non-Alcoholic Fatty Liver Disease; Type2 Diabetes
• Interventions: Drug: Liraglutide; Drug: Metformin; Drug: Gliclazide

• Registration Number: NCT03068065
• Lead Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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.

Study Timeline

• Study Start: 2014-05
• Primary Completion: 2014-11
• Study Completion: 2015-10
• Status Verified: 2017-02
• Study First Submitted: 2017-02-16
• Study First Submitted QC: 2017-02-28
• Last Update Submitted: 2017-02-28
• Study First Posted: 2017-03-01
• Last Update Posted: 2017-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 87

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Liraglutide	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
Metformin	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
Gliclazide	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

Primary Outcome Measures

Name	Time	Method
Intrahepatic fat	-7±3days; 168±3days	intrahepatic fat change from baseline by quantitative ultrasound

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University; 🇨🇳 Nanjing, Jiangsu, China