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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Controlled Trial Comparing Insulin Degludec and Glargine U100 for the Inpatient and Post-Hospital Discharge Management of Medicine and Surgery Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Degludec
* Drug: Glargine
* Drug: Aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females > 18 years of age who are admitted to a general medicine or surgical service 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 Subjects with diet alone and HbA1c>7.0% Medical and surgical patients expected to be admitted length of stay (LOS) longer than 2 days 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) Signed, informed consent and HIPAA documentation prior to any study procedures Exclusion Criteria: Subjects with increased BG concentration, but without a known history of diabetes (stress hyperglycemia) Subjects treated with diet alone (no antidiabetic agents) and admission HbA1c <7% Admission or pre-randomization BG≥400 mg/dL Subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria Patients treated with degludec or glargine U300, or with long-acting weekly GLP-1 RA (weekly exenatide, dulaglutide or albiglutide) 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) 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) 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 Known or suspected allergy to trial medication(s), excipients, or related products Previous participation in this trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degludec inpatient<br>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. | Drug: Degludec<br>* Degludec is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. Patients will be treated with bolus regimen given half of total daily dose (TDD) as basal once daily and half as aspart divided in three equal doses before meals. Patients with poor oral intake or with medical instruction to withhold oral intake (NPO) will receive the basal dose, but prandial dose will be held. Insulin dose will be adjusted daily to maintain a fasting and pre-dinner blood glucose (BG) between 100 mg/dL and 180 mg/dL.<br>* Other names: Tresiba;Drug: Aspart<br>* Aspart insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, aspart insulin dose will be held.<br>* Other names: Novolog;|
| Active Comparator: Glargine U100 inpatient<br>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. | Drug: Glargine<br>* Glargine is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. Patients will be treated with bolus regimen given half of total daily dose (TDD) as basal once daily and half as aspart divided in three equal doses before meals. Patients with poor oral intake or with medical instruction to withhold oral intake (NPO) will receive the basal dose, but prandial dose will be held. Insulin dose will be adjusted daily to maintain a fasting and pre-dinner BG between 100 mg/dL and 180 mg/dL.<br>* Other names: Lantus;Drug: Aspart<br>* Aspart insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, aspart insulin dose will be held.<br>* Other names: Novolog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Daily Blood Glucose Concentration in Hospitalized Patients | 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. | Baseline, up to the first 10 days of therapy | 
| Mean Daily Blood Glucose Concentration in Discharged Patients. | 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. | Day after hospital discharge to 4 weeks after discharge, 4 to 12 weeks after hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Blood Glucose Point-of-care Test Results Between 70 and 180 mg/dL in Hospitalized Patients | 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. | During the first 10 days of therapy | 
| Number of Participants With an Episode of Hypoglycemia While Hospitalized | 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. | During the first 10 days of therapy | 
| Number of Participants With an Episode of Clinically Significant Hypoglycemia While Hospitalized | 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. | During the first 10 days of therapy | 
| Number of Participants With an Episode of Severe Hypoglycemia While Hospitalized | 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. | During the first 10 days of therapy | 
| Number of Participants With an Episode of Severe Hyperglycemia While Hospitalized | 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. | During the first 10 days of therapy | 
| Daily Dose of Insulin in Hospitalized Patients | 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. | During the first 10 days of therapy | 
| Hemoglobin A1c (HbA1c) in Discharged Patients | 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. | 4 and 12 weeks after hospital discharge | 
| Number of Hypoglycemia Episodes in Discharged Patients | 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. | Up to 12 weeks after hospital discharge | 
| Number of Clinically Significant Hypoglycemia Episodes in Discharged Patients | 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. | Up to 12 weeks after hospital discharge | 
| Number of Episodes of Severe Hyperglycemia in Discharged Patients | 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. | Up to 12 weeks after hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long-acting insulin analog