Insulin Degludec and Glargine U100 for Management of Hospitalized and Discharged Patients With Type 2 Diabetes

Phase 4

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: Degludec; Drug: Glargine; Drug: Aspart

• Registration Number: NCT03336528
• Lead Sponsor: Emory University

Brief Summary

The purpose of this study is to find out if treatment with degludec insulin when compared to glargine U100 insulin will result in similar blood sugar control in patients with diabetes who are admitted to the hospital and then transition to home after discharge from the hospital.

Detailed Description

Degludec is a new generation basal insulin analog with a longer duration of action compared to insulin glargine. Several outpatient trials have reported that treatment with degludec results in comparable improvement in HbA1c levels and in lower rates of hypoglycemia compared to glargine U100 insulin. However, no previous studies have compared the safety and efficacy of the long-acting basal insulin degludec in the inpatient management of patients with diabetes. It is expected that a large number of patients with diabetes will be started on or transitioned to this new insulin formulation so acquiring knowledge on the safety and efficacy of degludec insulin is of great clinical interest. Accordingly, the proposed study will provide novel and clinically useful information on the efficacy (assessed as blood glucose control) and safety (assessed as hypoglycemia) of degludec in the inpatient setting and after hospital discharge in general medicine and surgery patients with Type 2 Diabetes (T2D).

Participants will be randomized to receive either a basal bolus with degludec or glargine U100 once daily during hospitalization. All participants will receive aspart insulin before meals. Participants with poorly controlled diabetes during the inpatient portion of the study will be invited to participate in the outpatient portion of the study. Participants in the outpatient portion of the study will be discharged on their preadmission oral antidiabetic medications plus degludec or glargine once daily, based on the study medication they were randomized to take during the inpatient portion of the study.

Study Timeline

• Study First Submitted: 2017-11-06
• Study First Submitted QC: 2017-11-06
• Study First Posted: 2017-11-08
• Study Start: 2018-01-02
• Primary Completion: 2021-03-01
• Study Completion: 2021-03-01
• Results First Submitted: 2022-02-25
• Status Verified: 2022-03
• Results First Submitted QC: 2022-03-25
• Last Update Submitted: 2022-03-25
• Results First Posted: 2022-03-31
• Last Update Posted: 2022-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Males or females > 18 years of age who are admitted to a general medicine or surgical service
2. A known history of T2D treated either with diet alone, oral monotherapy, any combination of oral antidiabetic agents, short-acting glucagon-like peptide-1 receptor agonists (GLP-1 RA) or insulin therapy except for degludec and glargine U300
3. Subjects with diet alone and HbA1c>7.0%
4. Medical and surgical patients expected to be admitted length of stay (LOS) longer than 2 days
5. Subjects must have a randomization BG > 140 mg and < 400 mg/dL without laboratory evidence of diabetic ketoacidosis (bicarbonate < 18 milliequivalent (mEq)/L, potential of hydrogen (pH) < 7.30, or positive serum or urinary ketones)
6. Signed, informed consent and HIPAA documentation prior to any study procedures

Read More

Exclusion Criteria

1. Subjects with increased BG concentration, but without a known history of diabetes (stress hyperglycemia)
2. Subjects treated with diet alone (no antidiabetic agents) and admission HbA1c <7%
3. Admission or pre-randomization BG≥400 mg/dL
4. Subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria
5. Patients treated with degludec or glargine U300, or with long-acting weekly GLP-1 RA (weekly exenatide, dulaglutide or albiglutide)
6. Patients with acute critical or surgical illness admitted to the ICU except for observation (<24 hours and did not require vasopressors and/or mechanical ventilation)
7. Patients with history of clinically relevant hepatic disease (diagnosed liver cirrhosis and portal hypertension), ongoing corticosteroid therapy (equal to a prednisone dose ≥5 mg/day), or impaired renal function (eGFR< 30 ml/min), or congestive heart failure (NYHA- IV)
8. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
9. Female subjects who are pregnant or breast feeding at time of enrollment into the study
10. Known or suspected allergy to trial medication(s), excipients, or related products
11. Previous participation in this trial

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Degludec inpatient	Degludec	Study participants treated with insulin prior to admission will receive 80% or 100% of the total daily dose (TDD) given as a basal bolus regimen with degludec once daily plus rapid-acting aspart insulin before meals.
Glargine U100 inpatient	Glargine	Study participants treated with insulin prior to admission will receive 80% or 100% of the total daily dose (TDD) given as basal bolus regimen with glargine once daily plus rapid-acting aspart insulin before meals.
Glargine U100 inpatient	Aspart	Study participants treated with insulin prior to admission will receive 80% or 100% of the total daily dose (TDD) given as basal bolus regimen with glargine once daily plus rapid-acting aspart insulin before meals.
Degludec inpatient	Aspart	Study participants treated with insulin prior to admission will receive 80% or 100% of the total daily dose (TDD) given as a basal bolus regimen with degludec once daily plus rapid-acting aspart insulin before meals.

Primary Outcome Measures

Name	Time	Method
Mean Daily Blood Glucose Concentration in Discharged Patients.	Day after hospital discharge to 4 weeks after discharge, 4 to 12 weeks after hospital discharge	Blood glucose was measured before each meal and at bedtime, after participants were discharged from the hospital. Mean daily blood glucose concentration was calculated to determine differences in outpatient glycemic control in patients with Type 2 Diabetes (T2D) treated with basal bolus regimen with insulin degludec or glargine once daily plus aspart insulin before meals. Information was collected via bi-weekly phone interviews and during the outpatient study visits at Weeks 4 and 12.
Mean Daily Blood Glucose Concentration in Hospitalized Patients	Baseline, up to the first 10 days of therapy	Blood glucose was measured before each meal and at bedtime among hospitalized study participants. Mean daily blood glucose concentration was calculated to determine differences in inpatient glycemic control in general medicine and surgery patients with Type 2 Diabetes (T2D) treated with basal bolus regimen with insulin degludec or glargine once daily plus aspart insulin before meals. A random (non-fasting) blood glucose measurement of 140 mg/dL or less is considered normal, while a measurement of 200 mg/dL or more indicates diabetes.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With an Episode of Clinically Significant Hypoglycemia While Hospitalized	During the first 10 days of therapy	Blood glucose was measured before each meal and at bedtime. The number of participants with at least one episode of clinically significant hypoglycemia, defined as BG \< 54 mg/dL, is presented here.
Number of Participants With an Episode of Severe Hypoglycemia While Hospitalized	During the first 10 days of therapy	Blood glucose as measured before each meal and at bedtime. The number of participants with at least one episode of severe hypoglycemia, defined as BG \< 40 mg/dL, is presented here.
Number of Participants With an Episode of Severe Hyperglycemia While Hospitalized	During the first 10 days of therapy	Blood glucose was measured before each meal and at bedtime. The number of participants who experienced at least one episode of severe hyperglycemia, defined as BG \> 240 mg/dL, is presented here.
Daily Dose of Insulin in Hospitalized Patients	During the first 10 days of therapy	Electronic medical records and nursing records documented the day day and time of insulin administration, including the basal study drug given once daily (degludec or glargine), prandial insulin given before meals (aspart), and supplemental insulin given to correct hyperglycemia. The mean daily doses of basal insulin, prandial insulin, and total daily dose of insulin given to hospitalized patients are presented here.
Number of Blood Glucose Point-of-care Test Results Between 70 and 180 mg/dL in Hospitalized Patients	During the first 10 days of therapy	Blood glucose was measured with point-of-care testing before each meal and at bedtime, and the count of blood glucose test results between 70 mg/dL and 180 mg/dL was determined.
Number of Participants With an Episode of Hypoglycemia While Hospitalized	During the first 10 days of therapy	Blood glucose (BG) was measured before each meal and at bedtime. The number of participants with at least one hypoglycemic episode, defined as BG of 54 to 70 mg/dL, is presented here.
Hemoglobin A1c (HbA1c) in Discharged Patients	4 and 12 weeks after hospital discharge	The HbA1C test reflects the average of a person's blood glucose levels over the past 3 months by measuring the percentage of red blood cells (RBCs) with glycated hemoglobin (hemoglobin with glucose bonded to it). Participants with HbA1C ≥ 7.5% were followed for 12 weeks after hospital discharge. Samples for HbA1C were drawn at 4 and 12 weeks post-discharge. An HbA1c measurement below 5.7% is considered normal, while a measurement of 6.5% or greater indicates diabetes.
Number of Hypoglycemia Episodes in Discharged Patients	Up to 12 weeks after hospital discharge	Blood glucose was measured before each meal and at bedtime. The number of hypoglycemia episodes, defined as BG \< 70 mg/dL, was recorded via bi-weekly phone interviews and during 4 and 12 week outpatient study visits.
Number of Clinically Significant Hypoglycemia Episodes in Discharged Patients	Up to 12 weeks after hospital discharge	Blood glucose will be measured before each meal and at bedtime. The number of episodes of clinically significant hypoglycemia, defined as BG \< 54 mg/dL, are presented here.
Number of Episodes of Severe Hyperglycemia in Discharged Patients	Up to 12 weeks after hospital discharge	Blood glucose was measured before each meal and at bedtime. The number of episodes of severe hyperglycemia, defined as BG \> 240 mg/dL, are presented here.

Trial Locations

Locations (4)

Emory University Hospital Clinical Research Network; 🇺🇸 Atlanta, Georgia, United States

Grady Hospital; 🇺🇸 Atlanta, Georgia, United States

Mount Sinai; 🇺🇸 New York, New York, United States

Providence Medical Research Centre; 🇺🇸 Spokane, Washington, United States