Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin) Therapy in the Inpatients With Type 2 Diabetes

High blood glucose levels in hospitalized patients with diabetes are associated with
increased risk of medical complications and death. Improved glucose control with insulin
injections may improve clinical outcome and prevent some of the hospital complications.
Glargine (Lantus®) insulin injection is the most common treatment of diabetes in the
hospital. Sitagliptin (Januvia®)is effective in lowering blood glucose, but has not been
tested in the hospital. It is not known if sitagliptin is as effective in controlling blood
sugars in the hospital. This study will compare sitagliptin by mouth, insulin (glargine)
injection, and the combination of sitagliptin and lantus insulin in controlling blood sugar
in hospitalized patients with diabetes.

In this pilot study, patients with known history of diabetes treated with diet and/or oral
anti-diabetics or with low total daily dose insulin therapy (<0.4 unit/kg/day) will be
randomized to receive sitagliptin once daily (group 1), sitagliptin plus basal (glargine)
insulin once daily (group 2), or basal bolus regimen with glargine once daily and lispro
insulin before meals (group 3). If needed, patients in the 3 treatment groups will receive
correction doses of rapid-acting lispro (Humalog®) insulin in the presence of hyperglycemia
(BG > 140 mg/dl) per sliding scale. The overall hypothesis is that treatment with sitagliptin
once daily alone or in combination with basal insulin in patients with type 2 diabetes will
result in a similar improvement in glycemic control and in a lower frequency of hypoglycemic
events than treatment with basal bolus insulin regimen with glargine once daily and lispro
insulin before meals.

A total of 90 subjects with type 2 diabetes will be recruited in this study. Patients will be
recruited at Grady Memorial Hospital and Emory University Hospital.

Inclusion Criteria:

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

2. A known history of type 2 diabetes mellitus > 3 months, receiving either diet alone,
oral antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination
therapy (excluding Trazodone (TZDs) and DPP4 inhibitors), or low-dose (≤ 0.4
units/kg/day) insulin therapy.

3. Subjects with a BG >140 mg and < 400 mg/dL without laboratory evidence of diabetic
ketoacidosis (serum bicarbonate < 18 milliequivalent /L or positive serum or urinary
ketones).

Exclusion Criteria:

1. Age < 18 or > 80 years.

2. Subjects with increased blood glucose concentration, but without a known 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. History of TZD treatment (pioglitazone or rosiglitazone) or DPP4 inhibitor
(sitagliptin or saxagliptin) during the past 3 months prior to admission.

5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to
require prolonged admission to a critical care unit (ICU, cardiac care unit , surgical
intensive care unit, neuro ICU).

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

7. Medical or surgical patients expected to be kept nil per os (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 congestive heart failure (NYHA class III and IV), acute myocardial
infarction, clinically significant hepatic disease or significantly impaired renal
function (serum creatinine ≥ 2.0 mg/dL).

10. Treatment with oral or injectable corticosteroid.

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.