Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes

Specific Aim 1: To determine whether in-hospital glycemic control, as measured by mean daily
blood glucose concentration and frequency of hypoglycemic events, is different between
treatment with sitagliptin (Januvia®) in combination with basal insulin (glargine) and basal
bolus regimen (glargine and rapid-acting insulin analog) in general medicine and surgery
patients with T2D. Patients with T2D treated with diet and/or OAD or with low total daily
dose insulin therapy (≤0.6 unit/kg/day) will be randomized to receive sitagliptin plus
glargine insulin (group 1) or basal bolus regimen with glargine once daily and rapid-acting
insulin (lispro or aspart) before meals (group 2). If needed, patients in the 2 treatment
groups will receive supplemental (correction) doses of rapid-acting insulin before meals for
BG > 140 mg/dl.

Specific Aim 2: To determine the efficacy and safety of an A1C based discharge algorithm in
controlling BG after discharge in patients with T2D. Patients who participate in the
in-hospital (Aim 1) arm will be invited to enroll in this open label prospective outpatient
study. The total duration of the study is 6 months. Patients with HbA1c ≤ 7% will be
discharged on the combination of metformin and sitagliptin (Janumet ®) twice daily. Those
with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ®)
twice daily plus glargine insulin at 50% of the inpatient glargine dose. Those with HbA1c >
9% will be discharged on metformin and sitagliptin (Janumet ®) twice-daily plus glargine
insulin at 80% of the inpatient dose.

Inclusion Criteria:

1. Males or females between the ages of 18 and 80 years admitted to medicine and surgery
services.

2. A known history of Type 2 Diabetes > 1 month, receiving either diet alone, oral
antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination
therapy (excluding DPP-4 inhibitors) or low-dose (≤ 0.6 units/kg/day) insulin
therapy.

3. Subjects with a blood glucose >140 mg and < 400 mg/dL at time of randomization
without laboratory evidence of diabetic ketoacidosis (serum bicarbonate < 18 mEq/L or
positive serum or urinary ketones).

Exclusion Criteria:

1. Age < 18 or > 80 years.

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

3. Subjects with a history of type 1 diabetes (suggested by BMI < 25 requiring insulin
therapy or with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic
state, or ketonuria) [46].

4. Treatment with DPP4 inhibitor or Glucagon like peptide 1 (GLP1) analogs during the
past 3 months prior to admission.

5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to
require admission to a critical care unit.

6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to
require gastrointestinal suction.

7. Medical or surgical patients expected to be kept NPO for >24-48 hours after admission
or after completion of surgical procedure.

8. Patients with clinically relevant pancreatic or gallbladder disease.

9. Patients with acute myocardial infarction, clinically significant hepatic disease or
significantly impaired renal function (GFR < 30 ml/min).

10. Treatment with oral or injectable corticosteroid = or > prednisone 5 mg/per day.

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

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