Exenatide Inpatient Trial: A Randomized Controlled Pilot Trial on the Safety and Efficacy of Exenatide (Byetta®) Therapy for the Inpatient Management of Patients With Type 2 Diabetes

The association between hyperglycemia and poor clinical outcomes in patients with diabetes is
well established. Data from previous trials in hospitalized patients have shown a strong
association between hyperglycemia and poor clinical outcomes, such as mortality, morbidity,
length of stay (LOS), infections and overall complications. Basal bolus insulin regimens
improve glycemic control and reduce the rate of hospital complications compared to sliding
scale regular insulin (SSRI). However, the use of basal bolus is labor intensive, requiring
multiple daily insulin injections, and has a significant risk of hypoglycemia. The
investigators will study if treatment with exenatide alone or in combination with basal
insulin will result in similar glycemic control and a lower frequency of hypoglycemia than
treatment with basal bolus in general non-Intensive Care Unit (non-ICU) patients with Type 2
Diabetes.

Inclusion Criteria:

1. A known history of Type 2 Diabetes receiving either diet alone or oral antidiabetic
drugs (OAD) including insulin secretagogues, pioglitazone, DPP4 inhibitors, or
metformin as monotherapy or in combination therapy, or low-dose insulin at <0.5
unit/kg/day.

2. Males or females between the ages of 18 and 80 years discharged after hospital
admission from general medicine and surgery services (non-Intensive Care Unit
setting).

3. Subjects with an admission / randomization BG < 400 mg/dL without laboratory evidence
of diabetic ketoacidosis (serum bicarbonate < 18 mEq/L or positive serum or urinary
ketones).

4. Admission HbA1c between 7% and 10%

5. BMI range: > 25 Kg/m^2 and < 45 Kg/m^2

Exclusion Criteria:

1. Age < 18 or > 80 years

2. Subjects with increased blood glucose (BG) concentration, but without a history of
diabetes (stress hyperglycemia)

3. Subjects with a history of type 1 diabetes (suggested by BMI < 25 Kg/m^2 requiring
insulin therapy or with a history of diabetic ketoacidosis and hyperosmolar
hyperglycemic state, or ketonuria).

4. Treatment with high-dose (>0.5 unit/kg/day) insulin or with GLP-1 RA during the past 3
months prior to admission.

5. Patients that required ICU care during the hospital admission.

6. Recurrent severe hypoglycemia or hypoglycemic unawareness.

7. Subjects with gastrointestinal obstruction, gastroparesis, history of pancreatitis or
those expected to require gastrointestinal suction.

8. Patients with clinically relevant pancreatic or gallbladder disease.

9. Patients with unstable or rapidly progressing renal disease or severe renal impairment
(creatinine clearance < 30 ml/min)

10. Patients with clinically significant hepatic disease (cirrhosis, jaundice, end-stage
liver disease),

11. History of hypersensitivity to exenatide

12. Treatment with oral or injectable corticosteroid (equal to a prednisone dose >5
mg/day), parenteral nutrition and immunosuppressive treatment.

13. Patients with history of heavy alcohol use (female > 2 drinks per day, male > 3 drinks
per day) or drug abuse within 3 months prior to admission.

14. Mental condition rendering the subject unable to understand the nature, scope, and
possible consequences of the study.

15. Female subjects who are pregnant or breast feeding at time of enrollment into the
study.