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

Condition(s) targeted: Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease

Intervention: Exenatide (Drug); insulin glargine (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Fudan University

Official(s) and/or principal investigator(s):
Xin Gao, doctor, Principal Investigator, Affiliation: Fudan University

Overall contact:
Hua Bian, doctor, Phone: 13681976102, Email: bian.hua@zs-hospital.sh.cn

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).

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in liver fat content（%） measured by MRS

Secondary outcome:

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

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 ≤ 9% 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

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 ≤ 9%

- 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.

Hua Bian, doctor, Phone: 13681976102, Email: bian.hua@zs-hospital.sh.cn

Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital, Shanghai, Shanghai, China; Not yet recruiting
Jia Lin Yang, doctor, Phone: 18918169025, Email: Jialinyang2002@163.com

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, Shanghai 200032, China; Not yet recruiting
Xin Gao, doctor, Phone: 862164041990, Ext: 8021, Email: gao.xin@zs-hospital.sh.cn
Hua Bian, doctor, Phone: 13681976102, Email: bian.hua@zs-hospital.sh.cn
Xin Gao, doctor, Principal Investigator
Hua Bian, doctor, Sub-Investigator
Lin Liu, master, Sub-Investigator

Department of Endocrinology and Metabolism,Huadong Hospital Affiliated to Fudan University, Shanghai, Shanghai, China; Not yet recruiting
Jiao Sun, Bachelor, Phone: 18621831253, Email: sunjiao6972@aliyun.com

Department of Endocrinology and Metabolism,Shanghai 6th People's Hospital, Shanghai, Shanghai, China; Not yet recruiting
Yu Qian Bao, Bachelor, Phone: 13788971763, Email: byq522@163.com

Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital, Shanghai, Shanghai, China; Not yet recruiting
Yong Quan Shi, master, Phone: 13701794075, Email: young.stone@163.com

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Starting date: December 2014
Last updated: November 28, 2014