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

NCT ID: NCT02455076

Last Updated: 2019-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2018-03-31

Brief 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.

Detailed 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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exenatide inpatient

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.

Group Type: ACTIVE_COMPARATOR

Exenatide

Intervention Type: DRUG

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.

Exenatide plus glargine insulin inpatient

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.

Group Type: ACTIVE_COMPARATOR

Exenatide

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

1. FBG >180 mg/dL, no hypoglycemia; glargine increased by 4 IU.

2. FBG >140 mg/dL, no hypoglycemia; glargine increased by 2 IU.

3. FBG 100-140 mg/dL, no hypoglycemia; no change in dosage.

4. FBG 70 - 99 mg/dl, decrease glargine by 4 IU or 10% of TDD.

5. FBG or RBG < 70 mg/dl, decrease glargine by 8 IU or 20% of TDD.

6. FBG or RBG < 40 mg/dl, decrease dose of glargine by 30%.

Basal bolus regimen inpatient

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.

Group Type: ACTIVE_COMPARATOR

Glargine

Intervention Type: DRUG

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.

1. FBG >180 mg/dL, no hypoglycemia; glargine increased by 4 IU.

2. FBG >140 mg/dL, no hypoglycemia; glargine increased by 2 IU.

3. FBG 100-140 mg/dL, no hypoglycemia; no change in dosage.

4. FBG 70 - 99 mg/dl, decrease glargine by 4 IU or 10% of TDD.

5. FBG or RBG < 70 mg/dl, decrease glargine by 8 IU or 20% of TDD.

6. FBG or RBG < 40 mg/dl, decrease dose of glargine by 30%.

Rapid-acting insulin analogs

Intervention Type: DRUG

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.

Exenatide outpatient

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.

Group Type: ACTIVE_COMPARATOR

Exenatide

Intervention Type: DRUG

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.

Insulin Only

Patients with Type 2 Diabetes will be treated with Insulin only

Group Type: ACTIVE_COMPARATOR

Glargine

Intervention Type: DRUG

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.

1. FBG >180 mg/dL, no hypoglycemia; glargine increased by 4 IU.

2. FBG >140 mg/dL, no hypoglycemia; glargine increased by 2 IU.

3. FBG 100-140 mg/dL, no hypoglycemia; no change in dosage.

4. FBG 70 - 99 mg/dl, decrease glargine by 4 IU or 10% of TDD.

5. FBG or RBG < 70 mg/dl, decrease glargine by 8 IU or 20% of TDD.

6. FBG or RBG < 40 mg/dl, decrease dose of glargine by 30%.

Rapid-acting insulin analogs

Intervention Type: DRUG

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.

Interventions

Exenatide

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.

Intervention Type: DRUG

Glargine

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.

1. FBG >180 mg/dL, no hypoglycemia; glargine increased by 4 IU.

2. FBG >140 mg/dL, no hypoglycemia; glargine increased by 2 IU.

3. FBG 100-140 mg/dL, no hypoglycemia; no change in dosage.

4. FBG 70 - 99 mg/dl, decrease glargine by 4 IU or 10% of TDD.

5. FBG or RBG < 70 mg/dl, decrease glargine by 8 IU or 20% of TDD.

6. FBG or RBG < 40 mg/dl, decrease dose of glargine by 30%.

Intervention Type: DRUG

Rapid-acting insulin analogs

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 Type: DRUG

Other Intervention Names

Byetta; Lantus

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Guillermo Umpierrez, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guillermo E Umpierrez, MD, CDE

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

References

Fayfman M, Galindo RJ, Rubin DJ, Mize DL, Anzola I, Urrutia MA, Ramos C, Pasquel FJ, Haw JS, Vellanki P, Wang H, Albury BS, Weaver R, Cardona S, Umpierrez GE. A Randomized Controlled Trial on the Safety and Efficacy of Exenatide Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes. Diabetes Care. 2019 Mar;42(3):450-456. doi: 10.2337/dc18-1760. Epub 2019 Jan 24.

Reference Type: DERIVED

PMID: 30679302 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00080596

Identifier Type: -

Identifier Source: org_study_id