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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02455076
Recruitment Status : Completed
First Posted : May 27, 2015
Results First Posted : June 20, 2019
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Guillermo Umpierrez, MD, Emory University

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Exenatide Drug: Glargine Drug: Rapid-acting insulin analogs Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Exenatide Inpatient Trial: A Randomized Controlled Pilot Trial on the Safety and Efficacy of Exenatide (Byetta®) Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes
Actual Study Start Date : September 2015
Actual Primary Completion Date : March 2018
Actual Study Completion Date : March 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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.
Drug: 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.
Other Name: Byetta

Active Comparator: 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.
Drug: 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.
Other Name: Byetta

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%.
Other Name: Lantus

Active Comparator: 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.
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%.
Other Name: Lantus

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.

Active Comparator: 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.
Drug: 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.
Other Name: Byetta

Active Comparator: Insulin Only
Patients with Type 2 Diabetes will be treated with Insulin only
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%.
Other Name: Lantus

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.




Primary Outcome Measures :
  1. Mean Daily Blood Glucose Concentration Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days. ]
    The levels of blood glucose (BG) will be measured before each meal and at bedtime using a glucose meter. Blood glucose will be measured at baseline and during the hospital stay (up to 10 days).

  2. Change in HbA1c Concentration Inpatient [ Time Frame: 12 weeks from discharge. ]
    The difference in the levels of HbA1c at discharge and at 12 weeks from discharge will be measured. The A1C test result is reported as a percentage. The higher the percentage, the higher a person's blood glucose levels have been. A normal A1C level is below 5.7 percent.


Secondary Outcome Measures :
  1. Mean Fasting Blood Glucose Levels Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days. ]
    The blood glucose levels prior to the patient's first meal of the day will be assessed using a glucose meter.

  2. Mean Premeal Blood Glucose Levels Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The blood glucose levels prior to each meal will using a glucose meter.

  3. Incidence of Hypoglycemic Events Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The number of patients with hypoglycemia (blood glucose levels < 70 mg/dL) will be recorded.

  4. Incidence of Hyperglycemic Events Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    Percent of readings with hyperglycemia (blood glucose levels > 240 mg/dL)

  5. Total Daily Dose of Insulin Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The total daily dose of insulin needed for glycemic control from baseline through the patient's hospital stay will be recorded.

  6. Average Number of Days of Hospital Stay [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The average number of days in the hospital for subjects will be calculated.

  7. Incidence of the Need for ICU Care Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The total number of patients who require transfer to the ICU will be recorded.

  8. Hospital Mortality [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The total number of subject deaths during hospital stay will be recorded.

  9. Hospital Complications [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The total number of subjects who experience hospital complications like nosocomial pneumonia, bacteremia, respiratory failure, acute renal failure, and wound infections (surgery patients) will be recorded. Nosocomial infections will be diagnosed based on standardized Centers for Disease Control (CDC) criteria.

  10. Incidence of Acute Kidney Injury Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The number of patients who experience acute kidney injury diagnosed by an increment in serum creatinine >0.5 mg/dL from admission value or 50% of baseline value will be recorded.

  11. Incidence of Gastrointestinal Adverse Events Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    The number of subjects who experience gastrointestinal side effects including nausea, vomiting and diarrhea will be recorded.

  12. Number of Patients With Severe Hypoglycemic Events Inpatient [ Time Frame: Duration of hospital stay, an expected average of 10 days ]
    Occurrences of hypoglycemia (blood glucose levels < 40 mg/dL) will be recorded.

  13. Incidence of Hospital Readmissions [ Time Frame: 12 weeks after discharge ]
    The number of patients who require readmission to the hospital from the time of discharge to 12 weeks after discharge will be recorded.

  14. Mean Fasting Blood Glucose Levels During Outpatient Period [ Time Frame: 12 weeks after discharge ]
    Fasting Blood Glucose Levels were measured using blood test

  15. Mean Daily Blood Glucose Concentration During Outpatient Period [ Time Frame: 12 weeks after discharge ]
    Mean Daily Blood Glucose Concentration will be calculated and recorded.

  16. The Number of Patients With Hypoglycemia Outpatient [ Time Frame: 12 weeks after discharge ]
    Occurrence of hypoglycemia (blood glucose levels < 70 mg) will be identified by blood test

  17. Number of Patients With Severe Hypoglycemic Events [ Time Frame: 12 weeks after discharge ]
    Occurrences of hypoglycemia (blood glucose levels < 40 mg/dL) will be detected by blood test

  18. Change in Body Weight [ Time Frame: Time of discharge, 12 weeks after discharge ]
    The change in Body Weight from discharge to 12 weeks after discharge will be recorded

  19. Change in Body Mass Index [ Time Frame: Discharge (after day 10 or hospital stay), 12 weeks after discharge 12 weeks after discharge ]
    The change in BMI from discharge to 12 weeks after discharge will be calculated

  20. Number of Patients Who Had Emergency Room Visits [ Time Frame: 12 weeks after discharge ]
    The number of patients who had emergency room visits from the time of discharge to 12 weeks after discharge will be recorded.

  21. Number of Hospital Readmissions [ Time Frame: 12 weeks after discharge ]
    Number of hospital readmissions during 12 weeks after discharge will be recorded

  22. Number of Acute Kidney Injury Events [ Time Frame: 12 weeks from discharge. ]
    Number of Acute Kidney Injury events will be recorded

  23. Number of Severe Gastrointestinal Adverse Events [ Time Frame: 12 weeks from discharge. ]
    Number of Severe (require hospitalization) Gastrointestinal Adverse Events

  24. Change in Systolic Blood Pressure [ Time Frame: Discharge (after day 10 or hospital stay), 12 weeks after discharge ]
    Change in Systolic Blood Pressure from the time of discharge to 12 weeks after discharge will be recorded

  25. Change in Heart Rate [ Time Frame: Discharge (after day 10 or hospital stay), 12 weeks after discharge ]
    Change in heart rate from the time of discharge to 12 weeks after discharge will be recorded

  26. Efficacy, Measured by HbA1c Levels and no Weight Gain [ Time Frame: 12 weeks from discharge. ]
    Number of patients who have an HbA1c <7.0% and no weight gain at 12 weeks from discharge will be recorded.

  27. Efficacy, Measured by HbA1c Levels and no Hypoglycemia [ Time Frame: 12 weeks from discharge. ]
    Number of patients who have an HbA1c <7.0% and no hypoglycemia at 12 weeks from discharge will be recorded.

  28. Change in Diastolic Blood Pressure [ Time Frame: Discharge (after day 10 or hospital stay), 12 weeks after discharge ]
    Change in Diastolic Blood Pressure from the time of discharge to 12 weeks after discharge will be recorded



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02455076


Locations
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United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Emory University Hospital
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
Investigators
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Principal Investigator: Guillermo E Umpierrez, MD, CDE Emory University
  Study Documents (Full-Text)

Documents provided by Guillermo Umpierrez, MD, Emory University:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Guillermo Umpierrez, MD, Professor, Emory University
ClinicalTrials.gov Identifier: NCT02455076    
Other Study ID Numbers: IRB00080596
First Posted: May 27, 2015    Key Record Dates
Results First Posted: June 20, 2019
Last Update Posted: June 20, 2019
Last Verified: May 2019
Keywords provided by Guillermo Umpierrez, MD, Emory University:
Hypoglycemia
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
Insulin, Short-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists