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
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Exenatide; Glargine; Rapid-acting insulin analogs
Intervention description: Exenatide is dispensed via a 1.2 mL prefilled pen with 250 mcg/mL solution for subcutaneous (s.c.) injection and will be administered twice daily starting at 5 mcg per dose, either in the abdomen, thigh or upper arm. Exenatide injections will be given within 60 minutes prior to morning and evening meals (or before the two main meals of the day, approximately 6 hours or more apart between doses). The exenatide dose will be increased to 10 mcg twice daily after 1 month based on clinical response.; Glargine will be given once daily, at the same time of day. If the BG is between 140-200 mg/dL, the dose will be 0.2 units/kg/day; for BG levels 201-400 mg/dL, the dose will be 0.25 units/kg/day. The patients will be discharged on glargine once daily at 50% of the hospital dose.The total daily dose (TDD) of glargine is based on the patient's fasting BG levels for the last 2 days.
FBG >180 mg/dL, no hypoglycemia; glargine increased by 4 IU.
FBG >140 mg/dL, no hypoglycemia; glargine increased by 2 IU.
FBG 100-140 mg/dL, no hypoglycemia; no change in dosage.
FBG 70 - 99 mg/dl, decrease glargine by 4 IU or 10% of TDD.
FBG or RBG < 70 mg/dl, decrease glargine by 8 IU or 20% of TDD.
FBG or RBG < 40 mg/dl, decrease dose of glargine by 30%.; If the BG levels are >140 mg/dL, rapid acting insulin analogs will be administered following the "supplemental/sliding scale" protocol. If a patient is able and expected to eat all or most of his/her meals, supplemental insulin will be administered before each meal and at bedtime following the "usual" dose of the sliding scale protocol. If a patient is not able to eat, supplemental insulin will be administered every 6 hours following the "sensitive" dose of the sliding scale. If the BG is 141-180 mg/dL, then 2,3 or 4 units of insulin will be given; for BG 181 - 220 mg/dL; the units of insulin will be 3, 4 or 6; for BG 221 - 260 mg/dL, the units of insulin will be 4,5 or 8; for BG 261 - 300 mg/dL, the units of insulin will be 5, 6 or 10; for BG 301 - 350, the insulin will be 6, 8 or 12 units; for BG 351 - 400 mg/dL, the units of insulin will be 7,10 or 14; for BG> 400 mg/dL, the insulin will be 8,12 or 16 units.
Intervention MeSH terms: Exenatide; Insulin, Short-Acting
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 150.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Hypoglycemia

Summary:

      The purpose of this study is to try and achieve similar glycemic control in general
      non-Intensive Care Unit (non-ICU) patients with Type 2 Diabetes with exenatide alone or in
      combination with basal insulin as compared to treatment with basal bolus insulin alone. The
      association between hyperglycemia and poor clinical outcomes in patients with diabetes is
      well established. Previous studies have shown that basal bolus insulin regimens improve
      glycemic control and reduce the rate of hospital complications compared to sliding scale
      regular insulin (SSRI) therapy, but has a significant risk of hypoglycemia. The investigators
      will compare the efficacy and safety of exenatide alone or in combination with basal insulin
      to control high blood glucose levels resulting in a lower risk of hypoglycemia.
    

Eligibility criteria:

        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.