Novolog vs. Fiasp Insulin in Non-critically Ill Hospitalized Patients With Type 2 Diabetes Mellitus (In-FI)

Comparison of Postprandial Glycemic Control in Non-critically Ill Hospitalized Patients With Type 2 Diabetes Mellitus Using Novolog vs. Fiasp Insulin: a Randomized Controlled Open Label Trial

Hyperglycemia affects 30-40% of hospitalized patients. Despite the fact that basal/bolus insulin therapy has been demonstrated to improve glycemic control and clinical outcomes in patients, achieving good glucose control remains a challenge.

This study examines the effects of Fiasp (a faster acting insulin) on blood sugars after meals compared to another type of insulin known as Novolog. The study will be performed in patients with type 2 diabetes admitted to the hospital, who are not in the intensive care unit, and who are being seen by the inpatient diabetes consult team. Eligible participants will be treated with Fiasp or Novolog injected multiple times a day before meals and at bedtime, in addition to a once daily injection of insulin glargine as basal insulin. Which type of meal time insulin (Fiasp vs Novolog) the subject gets is decided by chance, like the flip of a coin. Insulin doses will be started and titrated based on a protocol. All the subjects will wear a blinded continuous glucose monitoring (CGM)) sensor placed in their arm which they will wear for 72 hours during the study. The glucose values from the CGM, collected during the time it is worn, will be downloaded and compared to assess the response to the two different types of insulins - Fiasp and Novolog. The goal is to determine if Fiasp works as well as or better than Novolog in controlling blood sugars, particularly after meals, in the subjects of the study.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Treated With Insulin
• Intervention / Treatment: Drug: Insulin glargine; Drug: NovoLog; Other: Standard carbohydrate diet; Drug: Insulin Fiasp

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sara M Alexanian, MD; Phone Number: 617-638-8545; Email: sara.alexanian@bmc.org
• Study Contact Backup: Name: Zhihui Ju, MPH; Phone Number: 617-638-5921; Email: zhihui.ju@bmc.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. English-speaking
2. Males and female adult subjects admitted to Boston Medical Center to a medical or surgical floor.
3. Consultation by the Inpatient Diabetes Service at Boston Medical Center is required prior to consent.
4. Age ≥ 21 and <= 80 years.
5. Diagnosed with type 2 diabetes at least 180 days prior to screening.
6. Hyperglycemia during admission, as defined by a point of care and/or venous blood glucose ≥ 140 mg/dL.

7. Prior to admission subjects must be using one of the following for outpatient diabetes management:

   1. Insulin
   2. ≥ 2 oral/injectable agents
   3. One oral/injectable agent with a hemoglobin A1c of ≥ 8% within 3 months of enrollment.
8. Patients who are expected to remain hospitalized for a minimum of 48 hours following CGM sensor placement.
9. BMI <45 kg/m^2.
10. Subjects must have insulin glargine dosing planned at bedtime for the duration of the study period. Morning and afternoon dosing of insulin glargine are exclusionary.

Exclusion criteria:

1. Patients with a history of type 1 diabetes or late-onset autoimmune diabetes (LADA).
2. Treatment or plan for treatment with glucocorticoids during the index hospitalization.
3. Female patients who are pregnant (tested during hospitalization or screening) or breast-feeding during the hospitalization.
4. Patients admitted with the following conditions: diabetic ketoacidosis, hyperosmolar hyperglycemic state, solid organ transplantation, or coronary artery bypass surgery.
5. Prior diagnosis of gastroparesis or cirrhosis.
6. Acute or chronic kidney disease with a serum creatinine of ≥ 2 mg/dL at the time of screening.
7. Clinically significant nausea and/or vomiting or unable to consume more than 30 grams of carbohydrate at each meal.
8. Patients expected to receive nothing by mouth (NPO) for >24 hours.
9. Use of continuous or intermittent enteral feeding or parenteral nutrition.
10. Patient receiving aspirin and/or vitamin C during the hospitalization.
11. Any mental condition rendering the subject unable to provide informed consent.
12. Patients currently incarcerated.
13. Patients using >1 unit/kg/day of insulin prior to admission.
14. Insulin pump usage within the 2 weeks prior to or during admission.
15. Patients currently using real-time continuous glucose monitoring (CGM) or personal flash glucose monitoring system (FGM).
16. Patients with a history of an allergy to any of the types of insulin or one of the excipients in the insulin used in the study.

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: Group 2 insulin glargine and Fiasp; Group 2 will receive basal insulin glargine as dosed in Group 1. Meal insulin Fiasp dosing will be calculated the same way as Novolog dosing. If the premeal BG is ≥ 150 mg/dL, additional Fiasp will be administered based off the correctional scale at the same time as the prandial insulin.	Drug: Insulin glargine; Insulin glargine doses will be determined by calculating the total daily dose (TDD) of insulin and providing 50% of the TDD as follows: start at 0.5 units/kg/day and subtract 0.1 unit/kg/day for 70+ yrs of age, renal insufficiency, pancreatic deficiency and add 0.1 unit/kg/day if hemoglobin A1c in >10%; Other Names: Lantus®; Other: Standard carbohydrate diet; Standard carbohydrate diet as per usual hospital care (75g with each meal); Drug: Insulin Fiasp; Fiasp will be administered with each meal if premeal glucose is ≥ 150 mg/dL and at bedtime if glucose is ≥ 200 mg/dL by calculating an individualized insulin sensitivity factor for each subject per the following formula: 1500/total daily dose of insulin = sensitivity factor.; Other Names: Fiasp®
Active Comparator: Group 1 insulin glargine and Novolog; Group 1 will receive daily basal insulin glargine with a scheduled bolus of meal insulin Novolog. Meal Novolog will be dosed at the time the subject starts to eat. If the premeal blood glucose (BG) is ≥ 150 mg/dL, additional Novolog will be administered based off the correctional scale at the same time as the prandial insulin. The dose of Novolog will be administered by the floor nurse as per usual standard of care.	Drug: Insulin glargine; Insulin glargine doses will be determined by calculating the total daily dose (TDD) of insulin and providing 50% of the TDD as follows: start at 0.5 units/kg/day and subtract 0.1 unit/kg/day for 70+ yrs of age, renal insufficiency, pancreatic deficiency and add 0.1 unit/kg/day if hemoglobin A1c in >10%; Other Names: Lantus®; Drug: NovoLog; Novolog will be administered with each meal if premeal glucose is ≥ 150 mg/dL and at bedtime if glucose is ≥ 200 mg/dL by calculating an individualized insulin sensitivity factor for each subject per the following formula: 1500/total daily dose of insulin = sensitivity factor.; Other Names: NovoLog®; Other: Standard carbohydrate diet; Standard carbohydrate diet as per usual hospital care (75g with each meal)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial Glucose Control	Percent of time spent in the glycemic target range of 100-180 mg/dL in the 4 hour postprandial period will be assessed using a continuous glucose monitoring (CGM) system.	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic Control While Hospitalized	Percent of time spent in the glycemic target range of 100-180 mg/dL during the duration of the study will be assessed using a continuous glucose monitoring (CGM) system.	3 days
Percent of Time Spent in Glycemic Range of 70-140 mg/dL	Percent of time spent in the glycemic target range of 70-140 mg/dL during the duration of the study assessed using a continuous glucose monitoring (CGM) system.	3 days
Percent of Time Spent With Hypoglycemia During Hospitalization	The percent of time in three categories of hypoglycemia : <70 mg/dL, <54 mg/dL, and <40 mg/dL will be assessed using a CGM during hospitalization.	3 days
Percent of Nocturnal Time in Glycemic Target Range 100-180 mg/dL	The percent of nocturnal time (from 00.01 AM to 5:59 AM) in the glycemic target range of 100-180 mg/dL	3 days
Percent of Nocturnal Time Spent With Hypoglycemia	The percent of nocturnal time (from 00.01 AM to 5:59 AM) in three categories of hypoglycemia: <70 mg/dL, <54 mg/dL, and <40 mg/dL will be assessed using CGM.	3 days
Percent of Postprandial Time Spent With Level 1 Hyperglycemia	The percent of time spent in level 1 hyperglycemia (181-239 mg/dL) will be assessed using CGM in the 4 hour postprandial period.	4 hours postprandial
Percent of Postprandial Time Spent With Level 2 Hyperglycemia	The percent of time spent in level 2 hyperglycemia (>240 mg/dL) will be assessed using CGM in the 4 hour postprandial period.	4 hours postprandial
Percent of Postprandial Time Spent With Hypoglycemia	The percent of postprandial time in three categories of hypoglycemia will be assessed: <70 mg/dL, <54 mg/dL, and <40 mg/dL.	4 hours postprandial

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Sara M Alexanian, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Actual): May 27, 2023
• Study Completion (Actual): May 27, 2023

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: July 1, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Hypoglycemia; Hyperglycemia; Fiasp; Novolog; Continuous glucose monitor (CGM); Hemoglobin A1c
• 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; Insulin, Globin Zinc; Insulin Aspart; Insulin Glargine
• Other Study ID Numbers: H-39600

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: Yes