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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

Phase 4
Completed
Conditions
Type 2 Diabetes
Interventions
Drug: Exenatide
Drug: Glargine
Drug: Rapid-acting insulin analogs
Registration Number
NCT02455076
Lead Sponsor
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
150
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
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Exenatide plus glargine insulin inpatientGlarginePatients 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.
Basal bolus regimen inpatientGlarginePatients 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.
Basal bolus regimen inpatientRapid-acting insulin analogsPatients 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.
Insulin OnlyGlarginePatients with Type 2 Diabetes will be treated with Insulin only
Insulin OnlyRapid-acting insulin analogsPatients with Type 2 Diabetes will be treated with Insulin only
Exenatide inpatientExenatidePatients 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.
Exenatide plus glargine insulin inpatientExenatidePatients 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.
Exenatide outpatientExenatidePatients 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.
Primary Outcome Measures
NameTimeMethod
Mean Daily Blood Glucose Concentration InpatientDuration 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).

Change in HbA1c Concentration Inpatient12 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
NameTimeMethod
Average Number of Days of Hospital StayDuration of hospital stay, an expected average of 10 days

The average number of days in the hospital for subjects will be calculated.

Incidence of the Need for ICU Care InpatientDuration of hospital stay, an expected average of 10 days

The total number of patients who require transfer to the ICU will be recorded.

Hospital MortalityDuration of hospital stay, an expected average of 10 days

The total number of subject deaths during hospital stay will be recorded.

Hospital ComplicationsDuration 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.

Incidence of Acute Kidney Injury InpatientDuration 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.

Incidence of Gastrointestinal Adverse Events InpatientDuration 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.

Number of Patients With Severe Hypoglycemic Events InpatientDuration of hospital stay, an expected average of 10 days

Occurrences of hypoglycemia (blood glucose levels \< 40 mg/dL) will be recorded.

Incidence of Hospital Readmissions12 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.

Mean Fasting Blood Glucose Levels During Outpatient Period12 weeks after discharge

Fasting Blood Glucose Levels were measured using blood test

Mean Daily Blood Glucose Concentration During Outpatient Period12 weeks after discharge

Mean Daily Blood Glucose Concentration will be calculated and recorded.

Mean Fasting Blood Glucose Levels InpatientDuration 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.

Mean Premeal Blood Glucose Levels InpatientDuration of hospital stay, an expected average of 10 days

The blood glucose levels prior to each meal will using a glucose meter.

Incidence of Hypoglycemic Events InpatientDuration of hospital stay, an expected average of 10 days

The number of patients with hypoglycemia (blood glucose levels \< 70 mg/dL) will be recorded.

Incidence of Hyperglycemic Events InpatientDuration of hospital stay, an expected average of 10 days

Percent of readings with hyperglycemia (blood glucose levels \> 240 mg/dL)

Total Daily Dose of Insulin InpatientDuration 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.

The Number of Patients With Hypoglycemia Outpatient12 weeks after discharge

Occurrence of hypoglycemia (blood glucose levels \< 70 mg) will be identified by blood test

Number of Patients With Severe Hypoglycemic Events12 weeks after discharge

Occurrences of hypoglycemia (blood glucose levels \< 40 mg/dL) will be detected by blood test

Change in Body WeightTime of discharge, 12 weeks after discharge

The change in Body Weight from discharge to 12 weeks after discharge will be recorded

Change in Body Mass IndexDischarge (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

Number of Patients Who Had Emergency Room Visits12 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.

Number of Hospital Readmissions12 weeks after discharge

Number of hospital readmissions during 12 weeks after discharge will be recorded

Number of Acute Kidney Injury Events12 weeks from discharge.

Number of Acute Kidney Injury events will be recorded

Number of Severe Gastrointestinal Adverse Events12 weeks from discharge.

Number of Severe (require hospitalization) Gastrointestinal Adverse Events

Change in Systolic Blood PressureDischarge (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

Change in Heart RateDischarge (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

Efficacy, Measured by HbA1c Levels and no Weight Gain12 weeks from discharge.

Number of patients who have an HbA1c \<7.0% and no weight gain at 12 weeks from discharge will be recorded.

Efficacy, Measured by HbA1c Levels and no Hypoglycemia12 weeks from discharge.

Number of patients who have an HbA1c \<7.0% and no hypoglycemia at 12 weeks from discharge will be recorded.

Change in Diastolic Blood PressureDischarge (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

Trial Locations

Locations (2)

Emory University Hospital

🇺🇸

Atlanta, Georgia, United States

Grady Memorial Hospital

🇺🇸

Atlanta, Georgia, United States

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