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

August 24, 2019 updated by: Xin Gao, Fudan University

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
      • Shanghai, Shanghai, China
        • Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital
      • Shanghai, Shanghai, China
        • Department of Endocrinology and Metabolism,Huadong Hospital
      • Shanghai, Shanghai, China
        • Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital
      • Shanghai, Shanghai, China
        • Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Exenatide
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
Drug: Exenatide
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.
Other Names:
  • Byetta
Active Comparator: Insulin glargine
Insulin glargine subcutaneously, once daily, for 24 weeks
Drug: insulin glargine

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%.

Other Names:
  • Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in liver fat content（%） measured by MRS
Time Frame: baseline and 24 weeks
Change in liver fat content（%） measured by MRS
baseline and 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
baseline and 24 weeks
Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c)
Time Frame: baseline and 24 weeks
Change in glucose metabolism (fasting blood glucose, postprandial plasma glucose, HbA1c)
baseline and 24 weeks
Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL)
Time Frame: baseline and 24 weeks
Change in blood lipid profile (total cholesterol, triglyceride, HDL, LDL)
baseline and 24 weeks
Change in body weight,waist circumference and hip circumference
Time Frame: baseline and 24 weeks
Change in body weight,waist circumference and hip circumference
baseline and 24 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in cardiac function measured by echocardiography
Time Frame: baseline and 24 weeks
Change in cardiac function measured by echocardiography
baseline and 24 weeks
Change in β-cell function (fasting C-peptide, 2-hour postprandial C-peptide)
Time Frame: baseline and 24 weeks
Change in β-cell function (fasting C-peptide, 2-hour postprandial C-peptide)
baseline and 24 weeks
Change in liver enzymes and laboratory parameters (hematology, biochemical tests)
Time Frame: baseline and 24 weeks
Change in liver enzymes and laboratory parameters (hematology, biochemical tests)
baseline and 24 weeks
Incidence of hypoglycaemia events
Time Frame: up to 24 weeks
Incidence of hypoglycaemia events
up to 24 weeks
Incidence of adverse events（AEs）and Severe adverse events(SAEs)
Time Frame: up to 24 weeks
Incidence of adverse events（AEs）and Severe adverse events(SAEs)
up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Collaborators

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

Investigators

  • Principal Investigator: Xin Gao, doctor, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Actual)

November 1, 2017

Study Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

November 23, 2014

First Submitted That Met QC Criteria

November 28, 2014

First Posted (Estimate)

December 1, 2014

Study Record Updates

Last Update Posted (Actual)

August 28, 2019

Last Update Submitted That Met QC Criteria

August 24, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESR-14-10096

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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