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Diabetes Mellitus, Type 2Phase 4NCT02303730

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

A Phase 4 study testing Exenatide and insulin glargine in people with Diabetes Mellitus, Type 2 and Non-alcoholic Fatty Liver Disease, run by Fudan University at 5 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Exenatide and insulin glargine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
5 sitesChina
Study dates
Mar 2015to Nov 2017
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;

Who cannot join

  • 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
Show all 13Show fewer
  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

China5 sites

  • Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University

    Shanghai, Shanghai Municipality, 200032

  • Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital

    Shanghai, Shanghai Municipality

  • Department of Endocrinology and Metabolism,Huadong Hospital

    Shanghai, Shanghai Municipality

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

    Shanghai, Shanghai Municipality

  • Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital

    Shanghai, Shanghai Municipality

Other trials in China

About this study

Official title: 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).

Read the 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.

Being tested
Exenatide, insulin glargine
Keywords
Diabetes, Non-alcoholic Fatty Liver Disease
Medical subject headings
Diabetes Mellitus, Type 2, Non-alcoholic Fatty Liver Disease, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ExenatideDrug

    Also called Byetta

    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.

  • insulin glargineDrug

    Also called Lantus

    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%.

Study groups in NCT02303730
Study groupRoleWhat they receive
ExenatideExperimentalExenatide 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
Receives: Drug: Exenatide
Insulin glargineActive comparatorInsulin glargine subcutaneously, once daily, for 24 weeks
Receives: Drug: insulin glargine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in liver fat content（%） measured by MRS

    Change in liver fat content（%） measured by MRS

    Measured: baseline and 24 weeks

Secondary outcomes (4)

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

    Measured: baseline and 24 weeks

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

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

    Measured: baseline and 24 weeks

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

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

    Measured: baseline and 24 weeks

  4. Change in body weight,waist circumference and hip circumference

    Change in body weight,waist circumference and hip circumference

    Measured: baseline and 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2014 (estimated)
  2. Study startMar 2015
  3. Primary completionNov 2017
  4. Study completionNov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02303730
Sponsor's protocol ID
ESR-14-10096
Status last verified
Aug 2019
First submitted
23 Nov 2014
Last updated
28 Aug 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Xu W, Bi Y, Sun Z, Li J, Guo L, Yang T, Wu G, Shi L, Feng Z, Qiu L, Li Q, Guo X, Luo Z, Lu J, Shan Z, Yang W, Ji Q, Yan L, Li H, Yu X, Li S, Zhou Z, Lv X, Liang Z, Lin S, Zeng L, Yan J, Ji L, Weng J. Comparison of the effects on glycaemic control and beta-cell function in newly diagnosed type 2 diabetes patients of treatment with exenatide, insulin or pioglitazone: a multicentre randomized parallel-group trial (the CONFIDENCE study). J Intern Med. 2015 Jan;277(1):137-50. doi: 10.1111/joim.12293. Epub 2014 Aug 5.

    PubMed 25039675

  • Gupta NA, Mells J, Dunham RM, Grakoui A, Handy J, Saxena NK, Anania FA. Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway. Hepatology. 2010 May;51(5):1584-92. doi: 10.1002/hep.23569.

    PubMed 20225248

  • Sharma S, Mells JE, Fu PP, Saxena NK, Anania FA. GLP-1 analogs reduce hepatocyte steatosis and improve survival by enhancing the unfolded protein response and promoting macroautophagy. PLoS One. 2011;6(9):e25269. doi: 10.1371/journal.pone.0025269. Epub 2011 Sep 21.

    PubMed 21957486

  • Okerson T, Yan P, Stonehouse A, Brodows R. Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens. 2010 Mar;23(3):334-9. doi: 10.1038/ajh.2009.245. Epub 2009 Dec 17.

    PubMed 20019672

  • Cuthbertson DJ, Irwin A, Gardner CJ, Daousi C, Purewal T, Furlong N, Goenka N, Thomas EL, Adams VL, Pushpakom SP, Pirmohamed M, Kemp GJ. Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One. 2012;7(12):e50117. doi: 10.1371/journal.pone.0050117. Epub 2012 Dec 6.

    PubMed 23236362

  • Kenny PR, Brady DE, Torres DM, Ragozzino L, Chalasani N, Harrison SA. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol. 2010 Dec;105(12):2707-9. doi: 10.1038/ajg.2010.363. No abstract available.

    PubMed 21131943

  • Sathyanarayana P, Jogi M, Muthupillai R, Krishnamurthy R, Samson SL, Bajaj M. Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes. Obesity (Silver Spring). 2011 Dec;19(12):2310-5. doi: 10.1038/oby.2011.152. Epub 2011 Jun 9.

    PubMed 21660077

  • Shao N, Kuang HY, Hao M, Gao XY, Lin WJ, Zou W. Benefits of exenatide on obesity and non-alcoholic fatty liver disease with elevated liver enzymes in patients with type 2 diabetes. Diabetes Metab Res Rev. 2014 Sep;30(6):521-9. doi: 10.1002/dmrr.2561.

    PubMed 24823873

  • Juurinen L, Tiikkainen M, Hakkinen AM, Hakkarainen A, Yki-Jarvinen H. Effects of insulin therapy on liver fat content and hepatic insulin sensitivity in patients with type 2 diabetes. Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E829-35. doi: 10.1152/ajpendo.00133.2006. Epub 2006 Nov 7.

    PubMed 17090752

  • ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.

    PubMed 22686416

  • Liu L, Wang R, Gao J, Yan J, Zhang J, Zhang Z, Liu J, Lin H, Rao S, Yao X, Wu W, Bian H, Wang X, Guo S, Gao X, Yan H. Insulin Glargine is More Suitable Than Exenatide in Preventing Muscle Loss in Non-Obese Type 2 Diabetic Patients with NAFLD. Exp Clin Endocrinol Diabetes. 2023 Nov;131(11):583-588. doi: 10.1055/a-2145-1004. Epub 2023 Jul 31.

    PubMed 37524110

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Exenatide and insulin glargine in people with Diabetes Mellitus, Type 2 and Non-alcoholic Fatty Liver Disease, run by Fudan University at 5 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in liver fat content（%） measured by MRS (time frame: baseline and 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02303730, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.

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