Extended Release Exenatide Versus Placebo In Diabetic Patients With Type 4 Cardiorenal Syndrome

Primary Aim

Among adult individuals with type 2 diabetes mellitus (T2DM) and at risk for diastolic heart
failure (DHF) and mildly reduced renal filtration function (Type 4 cardiorenal syndrome), to
evaluate the quantitative impact on the MISS (myocardial injury summary score) cardiac
biomarker score, cardiac fibrosis by MRI, cardiac strain by ultrasonography and strain rate
imaging, and KISS (kidney injury summary score) kidney biomarker score after 38 weeks of
treatment with exenatide extended-release or placebo.

Secondary Aim

To evaluate the inter-relationships between demographic, clinical, and biochemical variables
(MISS score, KISS score) and of progressive cardiac fibrosis as assessed by MRI, strain-rate
imaging, and in adult individuals with T2DM and at risk for DHF (Type 4 cardiorenal
syndrome).

Inclusion Criteria:

- Age ≥ 18

- Type 2 diabetes mellitus with hemoglobin A1C 6.6-9.9% with or without the use of
insulin

- Estimated glomerular filtration rate (eGFR) between 50 and 90 ml/min/1.73 m2

Exclusion Criteria:

- Allergy or intolerance to gadolinium

- Implanted cardiac pacemaker, defibrillator, loop recorder, or other implanted metallic
device

- Any other metallic implanted device that is a contra-indication to MRI scanning

- eGFR < 50 ml/min/1.73 m2

- eGFR > 90 ml/min/1.73 m2

- Patient has ever been treated with an approved or investigational GLP-1 receptor
agonist e.g. BYETTA™ (exenatide), BYDUREON™ (Exenatide extended-release), VICTOZA™
(liraglutide), or taspoglutide

- Patient is enrolled in another experimental protocol which involves the use of an
investigational drug or device, or an intervention that would interfere with the
conduct of the trial.

- Disorders of iron metabolism

- Collagen vascular diseases

- Myocardial infarction

- Use of DDP4 inhibitors, and PPAR gamma agonists

- Pregnancy or planned pregnancy during the trial period

- Hemoglobin A1C of ≥ 10.0% or <6.6%

- Fasting glucose ≥ 260 mg/dl

- Clinically significant abnormal baseline laboratories

- Morbid obesity or body girth that prohibits the ability to undergo echocardiography or
MRI scanning with high-quality image results

- Renal transplantation

- Severe gastrointestinal, liver, or neurodegenerative disease

- Decompensated liver cirrhosis (Child-Pugh score >7)

- New York Heart Association Class III or IV heart failure

- Patients have alanine aminotransaminase (ALT) greater than 5 times the upper limit of
the reference range.

- Prior pancreatitis

- Personal or family history of medullary thyroid adenoma or carcinoma (MTC)

- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

- History of severe hypoglycemia

- Prior bariatric surgery