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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Degludec; Drug: Aspart; Drug: Glargine

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 Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital Clinical Research Network
    • Atlanta, Georgia, United States, 30308
      • Grady Hospital
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Medical Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Degludec inpatient; 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; 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.; Other Names: Tresiba; Drug: Aspart; 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.; Other Names: Novolog
Active Comparator: Glargine U100 inpatient; 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: Aspart; 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.; Other Names: Novolog; Drug: Glargine; 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.; Other Names: Lantus

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Cardiac Complications During Hospitalization	Cardiac complications during hospitalization were examined as a composite of complications, defined as myocardial infarction, cardiac arrhythmia requiring medical treatment, or cardiac arrest. The number of participants experiencing cardiac complications while hospitalized patients is presented here.	During the first 10 days of therapy
Number of Participants With Acute Kidney Injury During Hospitalization	Acute kidney injury defined as an increase in serum creatinine ≥ 0.3 mg/dL from baseline or ≥1.5 times baseline creatinine, per Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The number of participants experiencing acute kidney injury during hospitalization is presented here.	During the first 10 days of therapy
Length of Hospital Stay	The length of hospital in days is presented here.	Duration of hospital stay (an average of 10 days)
Number of Participants Who Died During Hospitalization	Hospital mortality is evaluated as the number of deaths among participants during hospitalization.	Duration of hospital stay (an average of 10 days)
Number of Participants Experiencing Acute Kidney Injury in Discharged Patients	Acute kidney injury defined as an increase in serum creatinine ≥ 0.3 mg/dL from baseline or ≥1.5 times baseline creatinine, per Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. The number of participants experiencing acute kidney injury after hospital discharge is presented here.	Up to 12 weeks after hospital discharge

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Novo Nordisk A/S

Publications and helpful links

General Publications

• Galindo RJ, Pasquel FJ, Vellanki P, Alicic R, Lam DW, Fayfman M, Migdal AL, Davis GM, Cardona S, Urrutia MA, Perez-Guzman C, Zamudio-Coronado KW, Peng L, Tuttle KR, Umpierrez GE. Degludec hospital trial: A randomized controlled trial comparing insulin degludec U100 and glargine U100 for the inpatient management of patients with type 2 diabetes. Diabetes Obes Metab. 2022 Jan;24(1):42-49. doi: 10.1111/dom.14544. Epub 2021 Sep 24.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2018
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: November 6, 2017
• First Submitted That Met QC Criteria: November 6, 2017
• First Posted (Actual): November 8, 2017

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Long-acting insulin analog
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin Aspart; Insulin Glargine
• Other Study ID Numbers: IRB00087816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The research team will share individual participant data that underlie the results reported in this study, after deidentification.
• IPD Sharing Time Frame: Data will be available for sharing starting 6 months after publication and up to 5 years after publication.
• IPD Sharing Access Criteria: Access will be given to researchers who provide a methodologically sound proposal to achieve the aims in their approved proposal. Proposals should be directed to geumpie@emory.edu. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No