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

Emory University

Status and phase: Completed; Phase 4

Conditions: Type 2 Diabetes

Treatments: Drug: Rapid-acting insulin analogs; Drug: Exenatide; Drug: Glargine

Study type: Interventional

Funder types: Other

Identifiers

NCT02455076

IRB00080596

Details and patient eligibility

About

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.

Full description

The association between hyperglycemia and poor clinical outcomes in patients with diabetes is well established. Data from previous trials in hospitalized patients have shown a strong association between hyperglycemia and poor clinical outcomes, such as mortality, morbidity, length of stay (LOS), infections and overall complications. Basal bolus insulin regimens improve glycemic control and reduce the rate of hospital complications compared to sliding scale regular insulin (SSRI). However, the use of basal bolus is labor intensive, requiring multiple daily insulin injections, and has a significant risk of hypoglycemia. The investigators will study if treatment with exenatide alone or in combination with basal insulin will result in similar glycemic control and a lower frequency of hypoglycemia than treatment with basal bolus in general non-Intensive Care Unit (non-ICU) patients with Type 2 Diabetes.

Enrollment: 150 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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150 participants in 5 patient groups

Exenatide inpatient

Active Comparator group

Description:

Patients with Type 2 Diabetes treated with diet, oral antidiabetic drugs, or with low-dose insulin will receive exenatide (Byetta®) twice daily. Supplemental (correction) doses of rapid-acting insulin analogs will be given for blood glucose levels \> 140 mg/dL per the sliding scale.

Treatment:

Drug: Exenatide

Exenatide plus glargine insulin inpatient

Active Comparator group

Description:

Patients with Type 2 Diabetes treated with diet, oral antidiabetic drugs, or with low-dose insulin will receive exenatide twice daily and glargine once daily. Glargine insulin will be given once daily at the same time. Supplemental (correction) doses of rapid-acting insulin analogs will be given for blood glucose levels \> 140 mg/dL per the sliding scale.

Treatment:

Drug: Glargine

Drug: Exenatide

Basal bolus regimen inpatient

Active Comparator group

Description:

Patients with Type 2 Diabetes treated with diet, oral antidiabetic drugs, or with low-dose insulin will receive the Basal Bolus Regimen with Glargine and Rapid-Acting Insulin Analogs. Patients treated with insulin previously will receive 80% of total home daily insulin dose as the basal bolus. Half of the total daily dose will be given as glargine and half as rapid-acting insulin analogs. Supplemental (correction) doses of rapid-acting insulin analogs will be given for blood glucose levels \> 140 mg/dL per the sliding scale.

Treatment:

Drug: Glargine

Drug: Rapid-acting insulin analogs

Exenatide outpatient

Active Comparator group

Description:

Patients with Type 2 Diabetes treated with diet, oral antidiabetic drugs, or with low-dose insulin will receive exenatide (Byetta®) twice daily. Supplemental (correction) doses of rapid-acting insulin analogs will be given for blood glucose levels \> 140 mg/dL per the sliding scale.

Treatment:

Drug: Exenatide

Insulin Only

Active Comparator group

Description:

Patients with Type 2 Diabetes will be treated with Insulin only

Treatment:

Drug: Glargine

Drug: Rapid-acting insulin analogs