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Exenatide Compared With Insulin Glargine to Change Liver Fat Content in Type 2 Diabetes

Primary Purpose

Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease

Status

Completed

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Exenatide

insulin glargine

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Diabetes, Non-alcoholic Fatty Liver Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female, 18 ≤ age ≤ 70 years old.
Newly diagnosed type 2 diabetes mellitus (WHO Diagnostic criteria for diabetes mellitus, 1999).
Patients with NAFLD, MRS measurement of liver fat content> 10%.
7% ≤ HbA1c ≤ 10%
No heavy drinking history within the last 5 years (alcohol intake: male < 20 g/d, female < 10 g/d)
HBsAg (-), hepatitis C virus antibody (HCV-Ab) (-)
BMI ≥ 24 kg/m2;

Exclusion Criteria:

Pregnancy, lactation, intended pregnancy, or failure to take adequate contraceptive measures taken (contraception measures including sterilization, intrauterine device, oral contraceptives, and persistent use of condoms).
Type 1 diabetes mellitus, gestational diabetes mellitus or other special types of diabetes.
Liver and renal dysfunction (ALT or aspartate aminotransferase(AST) is 2.5 times higher than the upper limit of normal, or total bilirubin is 1.5 times higher than the upper limit of normal, or Cr ≥ 115 μmol/L).
increased amylase (blood amylase is 2.5 times higher than the upper limit of normal) or presence of gastrointestinal disease.
Use of drugs that may affect liver fat content within one month before or during the trial period, such as glucocorticoids, thyroid hormone, etc.
Use of GLP-1 receptor agonist, dipeptidyl peptidase -4 (DPP-4) inhibitors or insulin within 3 months before enrolment
Presence of serious dyslipidemia or other endocrine diseases (hypothyroidism, hypothalamic-pituitary dysfunction, etc).
Fatty liver caused by viral hepatitis, drug, alcohol, Wilson disease or total parenteral nutrition.
Presence of liver cancer, infection, biliary tract disease or recently increased liver enzyme due to medication.
Participation in strenuous exercise or administration of any drugs that affect glucose metabolism.
History of pancreatitis, alcohol abuse, metal disorders or history of allergy to investigational drug.
Congestive heart failure defined as New York Heart Association (NYHA) class III or IV, unstable angina or myocardial infarction in recent 6 months.
Any situation that may affect the implementation or results of the study.

Sites / Locations

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital
Department of Endocrinology and Metabolism,Huadong Hospital
Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital
Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Exenatide

Insulin glargine

Arm Description

Exenatide 5 ug twice daily 1 hour before meal subcutaneously for 4 weeks, then add to 10 ug twice daily 1 hour before meal subcutaneously for another 20 weeks

Insulin glargine subcutaneously, once daily, for 24 weeks

Outcomes

Primary Outcome Measures

Change in liver fat content（%） measured by MRS

Secondary Outcome Measures

Change in intra-abdominal visceral fat content (cm2), abdominal subcutaneous fat content (cm2), and ratio between intra-abdominal visceral fat and subcutaneous fat area by MRI

Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c)

Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL)

Change in body weight,waist circumference and hip circumference

Full Information

NCT ID

NCT02303730

First Posted

November 23, 2014

Last Updated

August 24, 2019

Sponsor

Fudan University

Collaborators

Huadong Hospital, Shanghai Minhang Central Hospital, Shanghai 6th People's Hospital, Shanghai Changzheng Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02303730

Brief Title

Exenatide Compared With Insulin Glargine to Change Liver Fat Content in Type 2 Diabetes

Official Title

Exenatide BID Compared With Insulin Glargine to Change Liver Fat Content in Non-alcoholic Fatty-liver Disease Patients With Type 2 Diabetes

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

March 2015 (undefined)

Primary Completion Date

November 2017 (Actual)

Study Completion Date

November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fudan University

Collaborators

Huadong Hospital, Shanghai Minhang Central Hospital, Shanghai 6th People's Hospital, Shanghai Changzheng Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate whether exenatide is superior to insulin glargine (after 24 weeks) in reducing liver fat content (by MRS) in patients with newly diagnosed type 2 diabetes mellitus and concomitant non-alcoholic fatty-liver disease(NAFLD).

Detailed Description

This is a randomized, open-label, parallel-group, active controlled, multi-center clinical trial to investigate whether exenatide is superior to insulin glargine in reducing liver fat content in patients with newly diagnosed type 2 diabetes mellitus and concomitant NAFLD.Patients with type 2 diabetes and concomitant NAFLD from 18-70 years of age, with inadequate glycaemic control defined as 7% ≤ HbA1c ≤ 10% and BMI≥24kg/ m2 at the time of screening. Patients should be on diet and exercise but drug treatment naive, no use of any glucagon-like peptide-1(GLP-1) analogues or insulin within 3 months before enrolment.Patients will have an screening period 2 weeks, and a 24-week open label treatment period. All demographic data variables collected by descriptive analysis tests are used. Qualitative variables use absolute frequency and percentage, and numeric variables use average, mean, median, standard deviation, maximum, minimum, quartiles, etc. Unless specifically stated, statistical significance will be defined as P<0.05 in the whole analysis procedure.For the primary endpoint of this study, superiority test will be applied to the quantitative data of these two groups. For secondary and exploratory efficacy variables, difference test will be used to analyse repeated measurement data from two groups. For essential Safety parameters, difference test will be used to analyse the differences between two groups.The analysis of all primary and secondary endpoints of efficacy and safety must be based on the Full Analysis Set (FAS). As supporting evidence, the analysis of primary endpoint variables must also comply with the Pre-protocol (PPS) Analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease

Keywords

Diabetes, Non-alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

76 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Exenatide

Arm Type

Experimental

Arm Description

Exenatide 5 ug twice daily 1 hour before meal subcutaneously for 4 weeks, then add to 10 ug twice daily 1 hour before meal subcutaneously for another 20 weeks

Arm Title

Insulin glargine

Arm Type

Active Comparator

Arm Description

Insulin glargine subcutaneously, once daily, for 24 weeks

Intervention Type

Drug

Intervention Name(s)

Exenatide

Other Intervention Name(s)

Byetta

Intervention Description

The starting dose of exenatide is 5 ug bid, subcutaneously, for 4 weeks, followed by 10 ug bid, subcutaneously, for 20 weeks. If hypoglycaemia (blood glucose<2.9 mmol/l or < 3.9 mmol/l at least 2 times) or serious intolerance occurs, the dose will be adjusted to 5 ug bid, subcutaneously.

Intervention Type

Drug

Intervention Name(s)

insulin glargine

Other Intervention Name(s)

Lantus

Intervention Description

The starting dose of insulin glargine will depend upon the HbA1c level at screening(HbA1c <8% use 0.1 -0.2 U/kg per day;HbA1c >8% use 0.2 -0.3 U/kg per day). Dose adjustment protocol for insulin glargine (at least 3 determinations of fasting blood glucose per week): fasting blood glucose(FBG) > 180 mg/dL(10 mmol/l): add 4 U; FBG 140-180 mg/dL(7.8-10 mmol/l): add 2 U; FBG 126-139 mg/dL(7.0-7.8 mmol/l): add 1 U. If hypoglycemia, reduce insulin glargine by: blood glucose <70mg/dl（3.9mmol/l）: 10%-20%; blood glucose <40mg/dl（2.2mmol/l）: 20%-40%.

Primary Outcome Measure Information:

Title

Change in liver fat content（%） measured by MRS

Description

Change in liver fat content（%） measured by MRS

Time Frame

baseline and 24 weeks

Secondary Outcome Measure Information:

Title

Change in intra-abdominal visceral fat content (cm2), abdominal subcutaneous fat content (cm2), and ratio between intra-abdominal visceral fat and subcutaneous fat area by MRI

Description

Change in intra-abdominal visceral fat content (cm2), abdominal subcutaneous fat content (cm2), and ratio between intra-abdominal visceral fat and subcutaneous fat area by MRI

Time Frame

baseline and 24 weeks

Title

Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c)

Description

Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c)

Time Frame

baseline and 24 weeks

Title

Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL)

Description

Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL)

Time Frame

baseline and 24 weeks

Title

Change in body weight,waist circumference and hip circumference

Description

Change in body weight,waist circumference and hip circumference

Time Frame

baseline and 24 weeks

Other Pre-specified Outcome Measures:

Title

Change in cardiac function measured by echocardiography

Description

Change in cardiac function measured by echocardiography

Time Frame

baseline and 24 weeks

Title

Change in β-cell function (fasting C-peptide, 2-hour postprandial C-peptide)

Description

Change in β-cell function (fasting C-peptide, 2-hour postprandial C-peptide)

Time Frame

baseline and 24 weeks

Title

Change in liver enzymes and laboratory parameters (hematology, biochemical tests)

Description

Change in liver enzymes and laboratory parameters (hematology, biochemical tests)

Time Frame

baseline and 24 weeks

Title

Incidence of hypoglycaemia events

Description

Incidence of hypoglycaemia events

Time Frame

up to 24 weeks

Title

Incidence of adverse events（AEs）and Severe adverse events(SAEs)

Description

Incidence of adverse events（AEs）and Severe adverse events(SAEs)

Time Frame

up to 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female, 18 ≤ age ≤ 70 years old. Newly diagnosed type 2 diabetes mellitus (WHO Diagnostic criteria for diabetes mellitus, 1999). Patients with NAFLD, MRS measurement of liver fat content> 10%. 7% ≤ HbA1c ≤ 10% No heavy drinking history within the last 5 years (alcohol intake: male < 20 g/d, female < 10 g/d) HBsAg (-), hepatitis C virus antibody (HCV-Ab) (-) BMI ≥ 24 kg/m2; Exclusion Criteria: Pregnancy, lactation, intended pregnancy, or failure to take adequate contraceptive measures taken (contraception measures including sterilization, intrauterine device, oral contraceptives, and persistent use of condoms). Type 1 diabetes mellitus, gestational diabetes mellitus or other special types of diabetes. Liver and renal dysfunction (ALT or aspartate aminotransferase(AST) is 2.5 times higher than the upper limit of normal, or total bilirubin is 1.5 times higher than the upper limit of normal, or Cr ≥ 115 μmol/L). increased amylase (blood amylase is 2.5 times higher than the upper limit of normal) or presence of gastrointestinal disease. Use of drugs that may affect liver fat content within one month before or during the trial period, such as glucocorticoids, thyroid hormone, etc. Use of GLP-1 receptor agonist, dipeptidyl peptidase -4 (DPP-4) inhibitors or insulin within 3 months before enrolment Presence of serious dyslipidemia or other endocrine diseases (hypothyroidism, hypothalamic-pituitary dysfunction, etc). Fatty liver caused by viral hepatitis, drug, alcohol, Wilson disease or total parenteral nutrition. Presence of liver cancer, infection, biliary tract disease or recently increased liver enzyme due to medication. Participation in strenuous exercise or administration of any drugs that affect glucose metabolism. History of pancreatitis, alcohol abuse, metal disorders or history of allergy to investigational drug. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV, unstable angina or myocardial infarction in recent 6 months. Any situation that may affect the implementation or results of the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xin Gao, doctor

Organizational Affiliation

Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

Facility Name

Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital

City

Shanghai

State/Province

Shanghai

Country

China

Facility Name

Department of Endocrinology and Metabolism,Huadong Hospital

City

Shanghai

State/Province

Shanghai

Country

China

Facility Name

Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital

City

Shanghai

State/Province

Shanghai

Country

China

Facility Name

Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital

City

Shanghai

State/Province

Shanghai

Country

China

12. IPD Sharing Statement

Plan to Share IPD

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Exenatide Compared With Insulin Glargine to Change Liver Fat Content in Type 2 Diabetes

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