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

NCT02455076 | Completed Phase 4 Results DMC

• 1 other identifier: IRB00080596
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

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.

Conditions

Type 2 Diabetes

Keywords

Hypoglycemia

Outcome Measures

Primary Outcomes (2)

• Mean Daily Blood Glucose Concentration Inpatient

  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).

  Duration of hospital stay, an expected average of 10 days.

• Change in HbA1c Concentration Inpatient

  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.

  12 weeks from discharge.

Secondary Outcomes (28)

• Mean Fasting Blood Glucose Levels Inpatient

  Duration of hospital stay, an expected average of 10 days.

• Mean Premeal Blood Glucose Levels Inpatient

  Duration of hospital stay, an expected average of 10 days

• Incidence of Hypoglycemic Events Inpatient

  Duration of hospital stay, an expected average of 10 days

• Incidence of Hyperglycemic Events Inpatient

  Duration of hospital stay, an expected average of 10 days

• Total Daily Dose of Insulin Inpatient

  Duration of hospital stay, an expected average of 10 days

Study Arms (5)

Exenatide inpatient

ACTIVE COMPARATOR

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 plus glargine insulin inpatient

ACTIVE COMPARATOR

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; Drug: Glargine

Basal bolus regimen inpatient

ACTIVE COMPARATOR

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; Drug: Rapid-acting insulin analogs

Exenatide outpatient

ACTIVE COMPARATOR

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

Insulin Only

ACTIVE COMPARATOR

Patients with Type 2 Diabetes will be treated with Insulin only

Drug: Glargine; Drug: Rapid-acting insulin analogs

Interventions

Exenatide 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.

Also known as: Byetta

Exenatide inpatient; Exenatide outpatient; Exenatide plus glargine insulin inpatient

Glargine 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%.

Also known as: Lantus

Basal bolus regimen inpatient; Exenatide plus glargine insulin inpatient; Insulin Only

Rapid-acting insulin analogs 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.

Basal bolus regimen inpatient; Insulin Only

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).
• 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).
• Admission HbA1c between 7% and 10%
• BMI range: \> 25 Kg/m\^2 and \< 45 Kg/m\^2

You may not qualify if:

• Age \< 18 or \> 80 years
• Subjects with increased blood glucose (BG) concentration, but without a history of diabetes (stress hyperglycemia)
• 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).
• Treatment with high-dose (\>0.5 unit/kg/day) insulin or with GLP-1 RA during the past 3 months prior to admission.
• Patients that required ICU care during the hospital admission.
• Recurrent severe hypoglycemia or hypoglycemic unawareness.
• Subjects with gastrointestinal obstruction, gastroparesis, history of pancreatitis or those expected to require gastrointestinal suction.
• Patients with clinically relevant pancreatic or gallbladder disease.
• Patients with unstable or rapidly progressing renal disease or severe renal impairment (creatinine clearance \< 30 ml/min)
• Patients with clinically significant hepatic disease (cirrhosis, jaundice, end-stage liver disease),
• History of hypersensitivity to exenatide
• Treatment with oral or injectable corticosteroid (equal to a prednisone dose \>5 mg/day), parenteral nutrition and immunosuppressive treatment.
• 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.
• Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
• Female subjects who are pregnant or breast feeding at time of enrollment into the study.

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• 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.

  PMID: 30679302 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypoglycemia

Interventions

Exenatide; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Guillermo Umpierrez
• Organization: Emory University

geumpie@emory.edu

(404)778-1665

Study Officials

• Guillermo E Umpierrez, MD, CDE

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: May 27, 2015
• Study Start: September 1, 2015
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: June 20, 2019
• Results First Posted: June 20, 2019

Record last verified: 2019-05

Locations

US (2)