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

NCT02303730 | Completed Phase 4

• 1 other identifier: ESR-14-10096
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 5

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).

Conditions

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

Keywords

Diabetes; Non-alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• Change in liver fat content（%） measured by MRS

  Change in liver fat content（%） measured by MRS

  baseline and 24 weeks

Secondary Outcomes (4)

• 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)

  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

  baseline and 24 weeks

Other Outcomes (5)

• Change in cardiac function measured by echocardiography

  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)

  baseline and 24 weeks

Study Arms (2)

Exenatide

EXPERIMENTAL

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

Insulin glargine

ACTIVE COMPARATOR

Insulin glargine subcutaneously, once daily, for 24 weeks

Drug: insulin glargine

Interventions

Exenatide DRUG

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.

Also known as: Byetta

Exenatide

insulin glargine DRUG

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%.

Also known as: Lantus

Insulin glargine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.
• % ≤ 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead
• Huadong Hospital: collaborator
• Shanghai Minhang Central Hospital: collaborator
• Shanghai 6th People's Hospital: collaborator
• Shanghai Changzheng Hospital: collaborator

Study Sites (5)

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Department of Endocrinology and Metabolism, Shanghai Minhang Central Hospital

Shanghai, Shanghai Municipality, China

Location

Department of Endocrinology and Metabolism,Huadong Hospital

Shanghai, Shanghai Municipality, China

Location

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

Shanghai, Shanghai Municipality, China

Location

Department of Endocrinology and Metabolism,Shanghai Changzheng Hospital

Shanghai, Shanghai Municipality, China

Location

Related Publications (11)

• 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.

  PMID: 25039675 BACKGROUND

• 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.

  PMID: 20225248 BACKGROUND

• 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.

  PMID: 21957486 BACKGROUND

• 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.

  PMID: 20019672 BACKGROUND

• 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.

  PMID: 23236362 BACKGROUND

• 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.

  PMID: 21131943 BACKGROUND

• 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.

  PMID: 21660077 BACKGROUND

• 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.

  PMID: 24823873 BACKGROUND

• 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.

  PMID: 17090752 BACKGROUND

• 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.

  PMID: 22686416 BACKGROUND

• 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.

  PMID: 37524110 DERIVED

MeSH Terms

Conditions

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

Interventions

Exenatide; Insulin Glargine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Xin Gao, doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: vice-president

Study Record Dates

• First Submitted: November 23, 2014
• First Posted: December 1, 2014
• Study Start: March 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)