Study of the Effect of Sitagliptin on Glucose (Sugar) Metabolism in Patients With Heart Failure

Screening:

Patients will be screened based on existing clinic information regarding NYHA class and
heart failure characteristics. Patients will be approached in clinic after completing
clinical care for that visit regarding participation in this trial.

If the patient agrees to participate, informed consent will be obtained at this time.

At enrollment:

1. Patients will be queried as to whether they have undergone previous nuclear medicine
scans in the previous year in order to ensure that they do not exceed current standards
for total annual radiation exposure.

2. Undergo a baseline combined 18-FDG PET/13N-NH3 PET/CT to assess the heart's ability to
utilize blood sugar and coronary blood flow. This will take approximately 3-4 hours.
This is a nuclear medicine procedure which is commonly used to assess myocardial
viability as well as global heart function. It involves injection of a
radioisotope-labeled tracers (18-FDG and 13N-NH3) intravenously followed by the
measurement of myocardial uptake using a tomographic scanner. Venous blood samples
performed during a 75g oral glucose load during the 18-FDG portion will assist with
quantitation of myocardial glucose uptake and of measurements of insulin sensitivity.
Perfusion (13N-NH3) images will be repeated during infusion of adenosine 0.14 mg/kg/min
in order to assess coronary flow reserve. A computed tomography scan will be performed
at the same time as the baseline PET scan for attenuation correction. Blood draws to
measure changes in fasting insulin, blood sugar, lipid profile, and ADMA levels.
Approximately 45 cc or 3 tablespoons of blood will be drawn and saved for possible
future analysis.

18-FDG/13N-NH3 PET scans are routinely performed on patients with ischemic heart disease.
While this study will use standard protocol for these examinations, they are not currently
part of standard of care for nonischemic heart failure. However, they are important in
testing the hypothesis of this study.

3)Begin sitagliptin 100 mg daily for four weeks. If calculated creatinine clearance is 30-49
cc/min by the Cocroft-Gault formula, sitagliptin dose will be reduced to 50 mg daily for
four weeks as per manufacturer guidelines. There will be no placebo arm. This will be an
open-label study. Patients will be advised regarding potential side effects to prompt
notification of study personnel. They will be instructed to contact the investigators for
any concerns or evidence of adverse effects.

4) At four weeks: Repeat FDG/NH3 PET as above to compare to pre-treatment scan. This will
take approximately 3-4 hours. Blood draws to measure changes in fasting insulin, blood
sugar, lipid profile, and ADMA levels. Approximately 45 cc or 3 tablespoons of blood will be
drawn and saved for possible future analysis.

Inclusion Criteria:

1. Diagnosis of nonischemic dilated cardiomyopathy, current NYHA class I-III congestive
heart failure

2. Treatment with a stable comprehensive heart failure regimen for at least 3 months
(including beta-blockers and ACE-inhibitors or anigotensin receptor blockers unless
intolerant)

3. Age > 18 yrs

Exclusion Criteria:

1. Cardiomyopathy primarily due to one of the following:

1. Ischemic heart disease

2. Primary valvular lesion

3. Hypertrophic cardiomyopathy

2. Cardiac resynchronization within the last 3 months

3. Calculated creatinine clearance <30 ml/min or end-stage renal disease on dialysis.
Creatinine clearance will be determined by the Cockroft-Gault formula.

4. Diagnosis of diabetes mellitus by:

1. Diabetes previously diagnosed per patient history

2. 2 or more fasting glucose values > 125 mg/dl

5. History of heart transplantation

6. Pregnancy or active breast feeding

7. Hospitalization for decompensated heart failure within 30 days prior to enrollment.