Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes
Sitagliptin Therapy in Hospitalized Patients 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. In a recent pilot
 study aiming to determine differences in glycemic control between treatment with sitagliptin
 (Januvia®) alone or in combination with basal insulin and basal bolus regimen in general
 medicine and surgery patients with type 2 diabetes (T2D). The investigators found that
 treatment with sitagliptin alone or in combination with basal insulin resulted in similar
 glycemic control compared to basal bolus regimen.

 The investigators will conduct a prospective RCT aimed to determine the safety and efficacy
 of sitagliptin therapy for in-hospital and post-discharge management of general medicine and
 surgical patients with T2D. A total of 280 patients with known history of diabetes will be
 randomized to receive sitagliptin plus basal (glargine) insulin once daily (group 1), or
 basal bolus regimen with glargine once daily and aspart or lispro insulin before meals (group
 2). If needed, patients in the treatment groups will receive correction doses of rapid-acting
 insulin in the presence of hyperglycemia (BG > 140 mg/dl). The overall hypothesis is that
 treatment with sitagliptin in combination with basal insulin in patients with type 2 diabetes
 will result in a similar improvement in hospital and post-discharge 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.

 Patients will be recruited at Grady Memorial Hospital, Emory University Hospital, University
 of Michigan, Ohio State University and Temple University
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.