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

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

• Age < 18 or > 80 years.
• Subjects with increased BG concentration, but without a history of diabetes (stress hyperglycemia).
• 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].
• Treatment with DPP4 inhibitor or Glucagon like peptide 1 (GLP1) analogs during the past 3 months prior to admission.
• Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require admission to a critical care unit.
• Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction.
• Medical or surgical patients expected to be kept NPO for >24-48 hours after admission or after completion of surgical procedure.
• Patients with clinically relevant pancreatic or gallbladder disease.
• Patients with acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (GFR < 30 ml/min).
• Treatment with oral or injectable corticosteroid = or > prednisone 5 mg/per day.
• Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
• Female subjects are pregnant or breast feeding at time of enrollment into the study.