Antidiabetic Effects on Intrahepatic Fat

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)

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.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes; Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Liraglutide; Drug: Metformin; Drug: Gliclazide

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 Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2014
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): October 1, 2015

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 28, 2017
• First Posted (ACTUAL): March 1, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Metformin; Liraglutide; Gliclazide
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Liver Diseases; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Metformin; Gliclazide
• Other Study ID Numbers: ChiCTR-TRC-14004660

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED