Benefits of Insulin Supplementation for Correction of Hyperglycemia in Patients With Type 2 Diabetes

NCT ID: NCT02408120

Last Updated: 2023-09-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 226 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2019-12-11

Brief Summary

The purpose of this study is to test whether using extra doses of aspart insulin to correct blood sugars before meals improves the care of patients with type 2 diabetes in the hospital who are already receiving the standard of care treatment with glargine and aspart insulin injections to control blood sugar levels. Studies done in the past indicate that blood sugar levels are controlled on the standard treatment of insulin and that most patients do not need the small extra dose of insulin at bedtime. The investigators want to test if there is any benefit to giving patients extra doses of insulin during the day to correct the high blood sugars.

Detailed Description

The management of patients with Type 2 diabetes involves treatment with two different types of insulin injections to control blood sugar levels. The doses of the two types of insulins, glargine insulin and aspart insulin are adjusted daily through the hospital stay based on blood sugar levels. Many times, in addition to glargine and aspart insulin at meals, additional small doses of aspart insulin are given to correct high blood sugar levels. It has not been determined if using these extra doses of aspart insulin to correct blood sugars before meals improves care of the patients. Studies done in the past indicate that blood sugar levels are well controlled on the standard treatment of the two insulins and that most patients do not need the small extra dose of insulin at bedtime. This study will test if insulin supplementation improves glycemic control and prevents hypoglycemia in insulin treated patients with type 2 diabetes mellitus.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: NONE

Study Groups

Insulin Aspart for BG > 140 mg/dL

Subjects will consist of hospitalized patients with type 2 diabetes and be randomized to receive insulin glargine once daily and insulin aspart divided in three equal doses before meals. Supplemental insulin aspart will be given before meals and at bedtime to subjects with blood glucose (BG) levels \>140 mg/dL.

Group Type: ACTIVE_COMPARATOR

Insulin glargine

Intervention Type: DRUG

Half of total daily dose (TDD) will be given as insulin glargine and will be given once daily, at the same time of the day.

Daily insulin dose will be adjusted as follow:

• If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change
• If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day
• If the fasting and pre-dinner BG is >180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day
• If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day
• If a patient develops hypoglycemia (BG <70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

Insulin aspart

Intervention Type: DRUG

Half of total daily dose will be given as insulin aspart and in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, the dose of aspart will be held.

Daily insulin dose will be adjusted as follow:

• If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change
• If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day
• If the fasting and pre-dinner BG is >180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day
• If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day
• If a patient develops hypoglycemia (BG <70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

Supplemental insulin aspart

Intervention Type: DRUG

Insulin aspart will be administered following the supplemental insulin scale protocol.

For the arm receiving supplemental insulin aspart at BG levels greater than 140 mg/dL, then supplemental insulin scale is as follows:

• BG >141-180 mg/dL; 2-4 units of insulin aspart
• BG between 181-220 mg/dL; 3-6 units of insulin aspart
• BG between 221-260 mg/dL; 4-8 units of insulin aspart
• BG between 261-300 mg/dL; 5-10 units of insulin aspart
• BG between 301-350 mg/dL; 6-12 units of insulin aspart
• BG between 351-400 mg/dL; 7-14 units of insulin aspart
• BG > 400 mg/dL; 8-16 units of insulin aspart

For the arm receiving supplemental insulin aspart at BG levels greater than 260 mg/dL, then supplemental insulin scale is as follows:

• BG between 261-300 mg/dL; 5-10 units of insulin aspart
• BG between 301-350 mg/dL; 6-12 units of insulin aspart
• BG between 351-400 mg/dL; 7-14 units of insulin aspart
• BG > 400 mg/dL; 8-16 units of insulin aspart

Insulin Aspart for BG > 260 mg/dL

Subjects will consist of hospitalized patients with type 2 diabetes and be randomized to receive insulin glargine once daily and insulin aspart divided in three equal doses before meals. Supplemental insulin aspart will be given before meals and at bedtime to subjects with blood glucose (BG) levels \>260 mg/dL.

Group Type: ACTIVE_COMPARATOR

Insulin glargine

Intervention Type: DRUG

Half of total daily dose (TDD) will be given as insulin glargine and will be given once daily, at the same time of the day.

Daily insulin dose will be adjusted as follow:

• If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change
• If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day
• If the fasting and pre-dinner BG is >180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day
• If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day
• If a patient develops hypoglycemia (BG <70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

Insulin aspart

Intervention Type: DRUG

Half of total daily dose will be given as insulin aspart and in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, the dose of aspart will be held.

Daily insulin dose will be adjusted as follow:

• If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change
• If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day
• If the fasting and pre-dinner BG is >180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day
• If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day
• If a patient develops hypoglycemia (BG <70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

Supplemental insulin aspart

Intervention Type: DRUG

Insulin aspart will be administered following the supplemental insulin scale protocol.

For the arm receiving supplemental insulin aspart at BG levels greater than 140 mg/dL, then supplemental insulin scale is as follows:

• BG >141-180 mg/dL; 2-4 units of insulin aspart
• BG between 181-220 mg/dL; 3-6 units of insulin aspart
• BG between 221-260 mg/dL; 4-8 units of insulin aspart
• BG between 261-300 mg/dL; 5-10 units of insulin aspart
• BG between 301-350 mg/dL; 6-12 units of insulin aspart
• BG between 351-400 mg/dL; 7-14 units of insulin aspart
• BG > 400 mg/dL; 8-16 units of insulin aspart

For the arm receiving supplemental insulin aspart at BG levels greater than 260 mg/dL, then supplemental insulin scale is as follows:

• BG between 261-300 mg/dL; 5-10 units of insulin aspart
• BG between 301-350 mg/dL; 6-12 units of insulin aspart
• BG between 351-400 mg/dL; 7-14 units of insulin aspart
• BG > 400 mg/dL; 8-16 units of insulin aspart

Interventions

Insulin glargine

Half of total daily dose (TDD) will be given as insulin glargine and will be given once daily, at the same time of the day.

Daily insulin dose will be adjusted as follow:

• If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change
• If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day
• If the fasting and pre-dinner BG is >180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day
• If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day
• If a patient develops hypoglycemia (BG <70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

Intervention Type: DRUG

Insulin aspart

Half of total daily dose will be given as insulin aspart and in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, the dose of aspart will be held.

Daily insulin dose will be adjusted as follow:

• If the fasting and pre-dinner BG is between 100 - 140 mg/dL in the absence of hypoglycemia the previous day: no change
• If the fasting and pre-dinner BG is between 140 - 180 mg/dL in the absence of hypoglycemia: increase basal insulin by 10% every day
• If the fasting and pre-dinner BG is >180 mg/dL in the absence of hypoglycemia the previous day: increase basal insulin dose by 20% every day
• If the fasting and pre-dinner BG is between 70 - 99 mg/dL in the absence of hypoglycemia: decrease TDD (basal and prandial) insulin dose by 10% every day
• If a patient develops hypoglycemia (BG <70 mg/dL), the insulin TDD (basal and prandial) should be decreased by 20%.

Intervention Type: DRUG

Supplemental insulin aspart

Insulin aspart will be administered following the supplemental insulin scale protocol.

For the arm receiving supplemental insulin aspart at BG levels greater than 140 mg/dL, then supplemental insulin scale is as follows:

• BG >141-180 mg/dL; 2-4 units of insulin aspart
• BG between 181-220 mg/dL; 3-6 units of insulin aspart
• BG between 221-260 mg/dL; 4-8 units of insulin aspart
• BG between 261-300 mg/dL; 5-10 units of insulin aspart
• BG between 301-350 mg/dL; 6-12 units of insulin aspart
• BG between 351-400 mg/dL; 7-14 units of insulin aspart
• BG > 400 mg/dL; 8-16 units of insulin aspart

For the arm receiving supplemental insulin aspart at BG levels greater than 260 mg/dL, then supplemental insulin scale is as follows:

• BG between 261-300 mg/dL; 5-10 units of insulin aspart
• BG between 301-350 mg/dL; 6-12 units of insulin aspart
• BG between 351-400 mg/dL; 7-14 units of insulin aspart
• BG > 400 mg/dL; 8-16 units of insulin aspart

Intervention Type: DRUG

Other Intervention Names

Lantus (glargine); Novolog; Novolog

Eligibility Criteria

Inclusion Criteria

1. Subjects admitted to the hospital with acute or chronic medical illnesses or for elective and emergency surgical illness or trauma

2. Known history of Type 2 diabetes mellitus for >3 months

3. Treated with either diet alone, any combination of oral antidiabetic agents, non-insulin injectables or insulin therapy

4. Blood glucose levels between >140 mg and <400 mg/dL without laboratory evidence of diabetic ketoacidosis

Exclusion Criteria

1. Hyperglycemia without a history of diabetes

2. Subjects with acute critical illness admitted to the ICU or expected to require ICU admission

3. Subjects receiving continuous insulin infusion

4. Clinically relevant hepatic disease

5. Corticosteroid therapy

6. Serum creatinine ≥ 3.5 mg/dL and/or glomerular filtration rate (GFR) <30

7. Subjects unable to sign consent

8. Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Priyathama Vellanki

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Priyathama Vellanki, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

References

Vellanki P, Cardona S, Galindo RJ, Urrutia MA, Pasquel FJ, Davis GM, Fayfman M, Migdal A, Peng L, Umpierrez GE. Efficacy and Safety of Intensive Versus Nonintensive Supplemental Insulin With a Basal-Bolus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes: A Randomized Clinical Study. Diabetes Care. 2022 Oct 1;45(10):2217-2223. doi: 10.2337/dc21-1606.

Reference Type: DERIVED

PMID: 35675498 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00078695

Identifier Type: -

Identifier Source: org_study_id