Clinical trial NCT02455076: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: Hypoglycemia
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2015-05-27
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mean Daily Blood Glucose Concentration Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days.
measure: Change in HbA1c Concentration Inpatient
timeFrame: 12 weeks from discharge.
Secondary outcomes:
measure: Mean Fasting Blood Glucose Levels Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days.
measure: Mean Premeal Blood Glucose Levels Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Incidence of Hypoglycemic Events Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Incidence of Hyperglycemic Events Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Total Daily Dose of Insulin Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Average Number of Days of Hospital Stay
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Incidence of the Need for ICU Care Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Hospital Mortality
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Hospital Complications
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Incidence of Acute Kidney Injury Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Incidence of Gastrointestinal Adverse Events Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Number of Patients With Severe Hypoglycemic Events Inpatient
timeFrame: Duration of hospital stay, an expected average of 10 days
measure: Incidence of Hospital Readmissions
timeFrame: 12 weeks after discharge
measure: Mean Fasting Blood Glucose Levels During Outpatient Period
timeFrame: 12 weeks after discharge
measure: Mean Daily Blood Glucose Concentration During Outpatient Period
timeFrame: 12 weeks after discharge
measure: The Number of Patients With Hypoglycemia Outpatient
timeFrame: 12 weeks after discharge
measure: Number of Patients With Severe Hypoglycemic Events
timeFrame: 12 weeks after discharge
measure: Change in Body Weight
timeFrame: Time of discharge, 12 weeks after discharge
measure: Change in Body Mass Index
timeFrame: Discharge (after day 10 or hospital stay), 12 weeks after discharge 12 weeks after discharge
measure: Number of Patients Who Had Emergency Room Visits
timeFrame: 12 weeks after discharge
measure: Number of Hospital Readmissions
timeFrame: 12 weeks after discharge
measure: Number of Acute Kidney Injury Events
timeFrame: 12 weeks from discharge.
measure: Number of Severe Gastrointestinal Adverse Events
timeFrame: 12 weeks from discharge.
measure: Change in Systolic Blood Pressure
timeFrame: Discharge (after day 10 or hospital stay), 12 weeks after discharge
measure: Change in Heart Rate
timeFrame: Discharge (after day 10 or hospital stay), 12 weeks after discharge
measure: Efficacy, Measured by HbA1c Levels and no Weight Gain
timeFrame: 12 weeks from discharge.
measure: Efficacy, Measured by HbA1c Levels and no Hypoglycemia
timeFrame: 12 weeks from discharge.
measure: Change in Diastolic Blood Pressure
timeFrame: Discharge (after day 10 or hospital stay), 12 weeks after discharge
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Guillermo E Umpierrez, MD, CDE
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.