Effect of Exenatide on Liver and Heart Fat and Inflammation

Phase 4

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Exenatide; Drug: Glipizide

• Registration Number: NCT01951651
• Lead Sponsor: Baylor College of Medicine

Brief Summary

The purpose of this study is to examine the effect of exenatide on liver and heart (myocardial) fat and inflammation.

Detailed Description

Type 2 diabetics and insulin resistant individuals have an excess of fat in the liver which is not attributable to alcohol or other known causes of liver disease, a condition defined as nonalcoholic fatty liver disease (NAFLD). The fatty liver is insulin resistant. Individuals with a fatty liver are more likely to have excess intra-abdominal fat as well as a reduction in circulating plasma adiponectin levels. We have previously shown that type 2 diabetes and its associated Non Alcoholic Fatty Liver Disease (NAFLD) is characterized by increased hepatic fat content, decreased circulating adiponectin levels, and hepatic and peripheral (muscle) insulin resistance. Weight loss in humans with Non Alcoholic Fatty Liver Disease is associated with a decrease in hepatic fat content. Exenatide, an incretin based anti-diabetes therapy, enhances glucose-dependent insulin secretion and glucose-dependent suppression of inappropriately high glucagon secretion, improves glycemic control in patients with type 2 diabetes and is associated with weight loss. In rodent studies, exenatide reduces hepatic and myocardial fat and reduces vascular inflammation independent of changes in weight. Exenatide has also been shown to increase plasma adiponectin levels in humans and rodents. Furthermore type 2 diabetics are characterized by an increase in both hepatic and myocardial fat and left ventricular dysfunction, particularly diastolic dysfunction. However, the effect of exenatide therapy on liver and myocardial fat content, as well as left ventricular function in patients with type 2 diabetes has not been previously studied.

Study Timeline

• Study Start: 2010-04
• Primary Completion: 2012-10
• Study Completion: 2013-03
• Study First Submitted: 2013-09-24
• Study First Submitted QC: 2013-09-24
• Study First Posted: 2013-09-26
• Results First Submitted: 2016-02-19
• Results First Submitted QC: 2016-03-16
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-14
• Results First Posted: 2016-04-15
• Last Update Posted: 2016-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
2. Patients may be of either sex. Female patients must be non-lactating and must either be at least two years post-menopausal, or be using adequate contraceptive precautions.
3. Patients must range in age from 30 to 70 years, inclusive.
4. Patients must meet the American Diabetes Association (ADA) criteria (ADA 1997 Criteria: fasting plasma glucose greater than or equal to 126 mg/dl) for the diagnosis of type 2 diabetes mellitus.
5. Patients must be on diet therapy and/or metformin treatment for type 2 diabetes (stable dose)and have a fasting plasma glucose concentration between 126 and 260 mg/dl
6. Patients must have Hematocrit greater than 34 vol%.
7. Subjects whose body weight has been stable over the three months prior to study enrollment will be included.

Exclusion Criteria

1. Patients must not have type 1 diabetes.
2. Patients must not have a fasting plasma glucose greater than 260 mg/dl.
3. Patients must not have received a thiazolidinedione for at least 3 months prior to randomization.
4. Patients must not be on insulin treatment or have received insulin for more than one week within the previous year prior to entry. Patients should not be on sulfonylureas, sitagliptin, or exenatide treatment.
5. Patients taking systemic glucocorticoids or other medications known to affect glucose tolerance are excluded.
6. Patients taking medications that affect gastrointestinal motility will be excluded.
7. Patients with a history of Congestive Heart Failure, or clinically significant cardiac, liver or kidney disease (creatinine greater than 1.5 mg/dl).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exenatide	Exenatide	Exenatide 10 micrograms injected subcutaneously twice daily for 6 months
Glipizide	Glipizide	Glipizide 5 mg (tablet), one tablet twice daily orally for 6 months

Primary Outcome Measures

Name	Time	Method
Myocardial Fat Content	6 months	Myocardial fat content following intervention as measured by magnetic resonance imaging and spectroscopy (MRS) in patients with type 2 diabetes.
Hepatic Fat Content	6 months	Hepatic fat content following intervention in patients with type 2 diabetes

Secondary Outcome Measures

Name	Time	Method
Left Ventricular Ejection Fraction (LVEF)(%).	6 months	Left Ventricular Ejection Fraction following intervention as measured by magnetic resonance imaging in patients with type 2 diabetes.
Monocyte Inflammatory Protein Nuclear Factor Kappa-B (NFkappaB) (%)	6 months	The percentage change in monocyte inflammatory proteins NFkappaB (%) from baseline.

Trial Locations

Locations (1)

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States