Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT01364584
• Collaborator: Amylin Pharmaceuticals, LLC. (Industry), Eli Lilly and Company (Industry)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 50
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Previous research in our lab and others has established that type 2 diabetes (T2D) is associated with significantly impaired functional exercise capacity, a factor which is potentially associated with an increased risk of cardiovascular disease in those with type 2 diabetes. Of great concern, the majority of people with type 2 diabetes are sedentary and one possible reason may be that exercise, even at low levels, is perceived as being a harder effort than for nondiabetic people. Thus, treatments that may motivate patients with type 2 diabetes to be more physically active have great potential benefit.

Recent observational studies suggest that glucagon-like peptide-1 agents, such as exenatide, may have a beneficial effect on endothelial and cardiac function. Because these two factors have been shown to be associated with exercise dysfunction in type 2 diabetes, the investigators hypothesize that exenatide may improve exercise capacity in those with type 2 diabetes. The aims of this study are to (1) assess whether exenatide will improve functional exercise capacity in persons with type 2 diabetes and (2) investigate the effect of exenatide on specific metabolic, endothelial, cardiac and peripheral circulatory measures of function related to changes in exercise capacity. The Investigators primary hypothesis is that exenatide will improve functional exercise capacity in people with type 2 diabetes. Having a drug that improves exercise capacity could motivate patients to exercise more and hence be a significant benefit.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Exenatide; Drug: Placebo	N/A

Detailed Description

Subjects will come for a total of seven testing visits, including two screening visits, during which evaluations will take place. Visits are structured as follows:

Visits 1, 2 and 3 will be completed over a four-week period.

1. After subjects review the study and give consent for study participation, a history and physical exam will be performed. In addition, the Low-level Physical Activity Recall (LoPAR) questionnaire, pulmonary function testing, and vital signs will be performed.

2. Subjects will be asked to fast prior to visit 2. Blood and urine samples will be collected for measurement of glycosylated hemoglobin(HbA1C), fasting glucose, fasting insulin, free fatty acids and microalbuminuria (these measures will be covariates in the analyses). A dietary survey will be administered for food preferences for the three day study diet administered prior to visits 3, 4, 6 and 7. Dual Energy X-ray Absorptiometry (DXA) and body composition tests will be done to ensure that groups are weight similar (using fat-free mass). Autonomic nervous system testing, a resting electrocardiogram (EKG) and familiarization bicycle test will be performed.

3. Subjects will receive a three day study diet prior to visit 3. A resting and exercise EKG will be performed on the day of the visit. Patients will have measures made of cardiac function and endothelial function on visit 3 as well using plethysmography and cardiac echo. The peak aerobic capacity (VO2max) test will be performed. Vital signs will be taken at rest.

4. Randomization: Subjects will receive a three day study diet prior to visit 4. During visit four, arterial stiffness/endothelial function will be non-invasively measured by the Sphygmocor system. Subjects will have three constant-load tests to measure oxygen (VO2) kinetics where oxygen saturation (StO2) will be measured during exercise. A resting and exercise EKG and vital signs will be performed during the visit. Subjects will be randomized to either taking exenatide or placebo and all must have been taking metformin (1-2 grams /d) for at least 3 months. Exenatide will be titrated starting at 5 mcg twice per day for two weeks then moving to 10 mcg twice per day as tolerated and the placebo dose will match this titration. During the treatment phase subjects will be given a log to keep track of their blood glucose each day. Study coordinators will contact each subject weekly to obtain these values which will be checked by the study doctors and shared with the subject's primary care physician if adjustments in other medications need to be made.

5. Week 4: Visit 5 will consist of a physical exam with a clinician as well as a blood draw and check of vital signs during exenatide treatment.

6. Week 12: After 3 months of exenatide or placebo administration, the procedures of Visit 3 will be repeated as Visit 6. Additional testing to be performed during visit 6 include a physical exam performed by a study physician, DXA scan and body composition tests to monitor any changes in body composition (fat-free mass), blood work for lab tests listed in Visit 2 and the LoPAR questionnaire.

7. Week 13: During visit 7, the testing performed during visit 4 will be repeated after 3 months of exenatide or placebo administration.

Subjects will continue exenatide or placebo treatment while completing exit testing during Weeks 12 and 13.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Impact of Exenatide on Cardiovascular Exercise Performance in Type 2 Diabetes
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exenatide Pre-dosed inject-able pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months	Drug: Exenatide; Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID); Other Names: Byetta
Placebo Comparator: Placebo Pre-dosed inject-able pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months	Drug: Placebo; Subcutaneous injection 2.5 mcg-10 mcg BID

Outcome Measures

Primary Outcome Measures

1. Peak Oxygen Consumption (VO2 Peak) [Baseline and 3 months]

   Subjects' peak oxygen consumption (VO2 peak) will be tested on a stationary bike before and after 3 months of study medication or placebo.

Secondary Outcome Measures

1. Oxygen Uptake Kinetics Steady State Tau [Baseline and 3 months]

   Time to steady state oxygen consumption will be assessed in subject before and after 3 months of study medication or placebo.

2. Change From Baseline in Arterial Stiffness [Baseline and 3 months]

   Pulse wave velocity will be measured via sphygmocor before and after 3 months of study medication or placebo.

3. Change From Baseline in Peak Dilation of Brachial Artery Diameter [Baseline and 3 months]

   Change in the response of the brachial artery to hyperemia will be assessed before and after 3 months of study medication or placebo.

4. Change in (Non-invasively Measured) Deoxygenated Hemoglobin Concentration in the Vastus Lateralis During Exercise [Baseline and 3 months]

   Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of study drug administration.

5. Echocardiographic Measures - Circumferential Strain [Baseline and 3 months]

   Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

6. Echocardiographic Measures - Longitudinal Strain [Baseline and 3 months]

   Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

7. Echocardiographic Measures - Stroke Volume [Baseline and 3 months]

   Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

8. Echocardiographic Measures - Mitral Valve E Wave Velocity [Baseline and 3 months]

   Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

9. Echocardiographic Measures - Mitral Valve E:A Wave Velocity [Baseline and 3 months]

   Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

10. Echocardiographic Measures - Mitral Valve Deceleration Time [Baseline and 3 months]

    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

11. Echocardiographic Measures - Septal E' [Baseline and 3 months]

    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

12. Echocardiographic Measures - Septal E:E' [Baseline and 3 months]

    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

13. Echocardiographic Measures - Lateral E' [Baseline and 3 months]

    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

14. Echocardiographic Measures - Lateral E:E' [Baseline and 3 months]

    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Men and women between the ages of 45 and 70 years of age

• Diagnosed with uncomplicated type 2 diabetes

• Sedentary persons (exercising not more than one time per week)

• Females who are post-menopausal

• BMI must be less than 35

• Subjects must be taking metformin for diabetes control and may also be on sulfonylurea drugs or meglitinides

• Glycosylated hemoglobin (HbA1C) <9%

• Non-smokers or former smokers who have quit for at least 1 year

• Absence of comorbid conditions

• Resting systolic blood pressure < 190, Resting diastolic blood pressure < 95

Exclusion Criteria

• People with type 2 diabetes (T2D) taking oral medications, other than metformin or sulfonylurea drugs or meglitinides, to control their diabetes.

• Persons treated with insulin will be excluded

• People who are currently smoking or have not quit for at least one year

• Peripheral neuropathy

• Regional wall motion abnormalities

• Left ventricular systolic dysfunction

• Ischemic heart disease (abnormal resting or exercise electrocardiogram)

• Presence of angina that would limit exercise performance

• Pulmonary problems that would limit exercise performance

• Systolic blood pressure >190 mmHg at rest or >250 mmHg with exercise or diastolic pressure >95 mmHg at rest or >115 mmHg with exercise

• Persons with autonomic dysfunction (>20 mm fall in upright BP without a change in heart rate)

• Proteinuria (urine protein >200 mg/dl) or a creatinine > 2.0 mg/dl

• Renal disease

• Persons with peripheral arterial disease

• Persons with a history of pancreatitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• Amylin Pharmaceuticals, LLC.
• Eli Lilly and Company

Investigators

• Principal Investigator: Judith G Regensteiner, PhD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01364584
• Other Study ID Numbers: 10-0438
• First Posted: Jun 2, 2011
• Last Update Posted: Aug 15, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Exenatide

Study Results

Participant Flow

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Period Title: Overall Study
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Exenatide	Placebo	Total
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID	Total of all reporting groups
Overall Participants	11	12	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (7)	64 (1)	64 (4)
Sex: Female, Male (Count of Participants)
Female	4 36.4%	7 58.3%	11 47.8%
Male	7 63.6%	5 41.7%	12 52.2%
Region of Enrollment (Count of Participants)
United States	11 100%	12 100%	23 100%
Body Mass (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	101.7 (5.3)	87.9 (3.3)	93.4 (16.1)
Body Mass Index (kg/m2) (kilograms per meter squared) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter squared]	33.9 (1.0)	31.3 (1.2)	32.3 (3.9)
Body Fat (%) (percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage]	37.7 (2.3)	35.7 (2.2)	36.7 (7.15)
Lean Mass (kg) (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	61.9 (3.9)	55.8 (2.8)	58.1 (11.6)
Fasting Glucose (mg/dl) (milligrams per deciliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per deciliter]	170.5 (24.2)	127.9 (8.0)	147.6 (59.9)
Fasting Insulin (μU/ml) (microunits per milliliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [microunits per milliliter]	29.0 (3.7)	34.6 (6.4)	31.0 (15.1)
HbA1c (%) (percentage of glycated hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycated hemoglobin]	7.3 (1.1)	7.2 (0.4)	7.2 (1.1)
Total Cholesterol (mg/dl) (milligrams per deciliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per deciliter]	156.3 (9.8)	175.3 (11.7)	165.2 (34.9)
LDL Cholesterol (mg/dl) (milligrams per deciliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per deciliter]	93.8 (6.2)	97.6 (7.4)	94.4 (22.1)
Triglycerides (mg/dl) (milligrams per deciliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per deciliter]	156.8 (18.3)	217.8 (58.0)	190.1 (136.9)
Glycerol (mg/dl) (milligrams per deciliter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligrams per deciliter]	1.21 (0.5)	1.14 (0.5)	1.16 (0.5)
Free Fatty Acids (mmol/L) (millimoles per liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimoles per liter]	580.8 (76.3)	500.5 (67.8)	546.3 (228.2)
VO2peak (ml/kg/min) (milliliters per kilogram per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters per kilogram per minute]	17.5 (1.0)	15.4 (0.9)	16.4 (3.1)
VO2peak (ml/min) (milliliters per minute) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters per minute]	1783 (129)	1363 (95)	1554 (415)
VO2 kinetics tau (sec) (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	78.2 (6.8)	63.3 (5.9)	71.9 (19.1)
Circumferential Strain (percentage difference in circumferences) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage difference in circumferences]	-23.7 (5.5)	-23.5 (5.0)	-23.6 (5.3)
Longitudinal Strain (percentage difference in lengths) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage difference in lengths]	-17.1 (3.9)	-19.3 (2.3)	-18.2 (3.4)
Stroke Volume (ml/beat) (milliliters per beat) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milliliters per beat]	79.2 (22.7)	82.5 (23.1)	81.5 (23.1)

Outcome Measures

1. Primary Outcome

Title	Peak Oxygen Consumption (VO2 Peak)
Description	Subjects' peak oxygen consumption (VO2 peak) will be tested on a stationary bike before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [milliliters per kilogram per minute]	16.6 (1.1)	16.1 (1.1)

2. Secondary Outcome

Title	Oxygen Uptake Kinetics Steady State Tau
Description	Time to steady state oxygen consumption will be assessed in subject before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [seconds]	71.4 (8.5)	67.2 (2.7)

3. Secondary Outcome

Title	Change From Baseline in Arterial Stiffness
Description	Pulse wave velocity will be measured via sphygmocor before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

Data unable to be collected on all participants, hence the difference between the overall number of participants analyzed here and the actual number of participants who completed the study

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed inject-able pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed inject-able pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	6	7
Mean (Standard Deviation) [meters/second]	-1.23 (1.27)	0.37 (0.89)

4. Secondary Outcome

Title	Change From Baseline in Peak Dilation of Brachial Artery Diameter
Description	Change in the response of the brachial artery to hyperemia will be assessed before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Pre-Intervention (Baseline)	0.193 (0.045)	0.192 (0.046)
Post-Intervention (3 months)	0.226 (0.057)	0.151 (0.026)

5. Secondary Outcome

Title	Change in (Non-invasively Measured) Deoxygenated Hemoglobin Concentration in the Vastus Lateralis During Exercise
Description	Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of study drug administration.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	0	0

6. Secondary Outcome

Title	Echocardiographic Measures - Circumferential Strain
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [% difference in circumferences]	-25.6 (1.78)	-22.6 (1.4)

7. Secondary Outcome

Title	Echocardiographic Measures - Longitudinal Strain
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [% difference in lengths]	-18.5 (1.2)	-18.3 (0.8)

8. Secondary Outcome

Title	Echocardiographic Measures - Stroke Volume
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [mL/beat]	93.3 (2.8)	80.7 (1.9)

9. Secondary Outcome

Title	Echocardiographic Measures - Mitral Valve E Wave Velocity
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [centimeters/second]	0.61 (0.06)	0.78 (0.06)

10. Secondary Outcome

Title	Echocardiographic Measures - Mitral Valve E:A Wave Velocity
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [centimeters/second]	0.85 (0.09)	0.82 (0.06)

11. Secondary Outcome

Title	Echocardiographic Measures - Mitral Valve Deceleration Time
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [milliseconds]	234.6 (17.0)	239.8 (14.6)

12. Secondary Outcome

Title	Echocardiographic Measures - Septal E'
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [centimeters/second]	0.08 (0.01)	0.07 (0.01)

13. Secondary Outcome

Title	Echocardiographic Measures - Septal E:E'
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [ratio]	8.3 (0.9)	12.6 (1.4)

14. Secondary Outcome

Title	Echocardiographic Measures - Lateral E'
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [centimeters/second]	0.09 (0.01)	0.09 (0.01)

15. Secondary Outcome

Title	Echocardiographic Measures - Lateral E:E'
Description	Potential change in cardiac function will be assessed by echocardiography before and after 3 months of study medication or placebo.
Time Frame	Baseline and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Exenatide	Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
Measure Participants	11	12
Mean (Standard Deviation) [ratio]	6.7 (0.6)	8.4 (1.2)

Adverse Events

Arm/Group Title	Exenatide		Placebo
Arm/Group Description	Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of exenatide for 2.5 months Exenatide: Subcutaneous injection 2.5 micrograms (mcg) to 10 mcg twice per day (BID)		Pre-dosed injectable pen (an automatic device which injects under the skin) 10 mcg twice a day of placebo for 2.5 months Placebo: Subcutaneous injection 2.5 mcg-10 mcg BID
All Cause Mortality
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		0/12 (0%)
Blood and lymphatic system disorders
Eosinophil count increased	1/11 (9.1%)		0/12 (0%)
Renal and urinary disorders
Renal Neoplasm (Tumor on base of kidney)	1/11 (9.1%)		0/12 (0%)
Bladder Papilloma	1/11 (9.1%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Exenatide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.