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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Treated With Insulin

Intervention / Treatment
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* Drug: Insulin glargine
* Drug: NovoLog
* Drug: Insulin Fiasp
* Other: Standard carbohydrate diet


Participation Criteria
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Eligibility Criteria
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Inclusion criteria English-speaking Males and female adult subjects admitted to Boston Medical Center to a medical or surgical floor. Consultation by the Inpatient Diabetes Service at Boston Medical Center is required prior to consent. Age ≥ 21 and <= 80 years. Diagnosed with type 2 diabetes at least 180 days prior to screening. Hyperglycemia during admission, as defined by a point of care and/or venous blood glucose ≥ 140 mg/dL. Prior to admission subjects must be using one of the following for outpatient diabetes management: Insulin ≥ 2 oral/injectable agents One oral/injectable agent with a hemoglobin A1c of ≥ 8% within 3 months of enrollment. Patients who are expected to remain hospitalized for a minimum of 48 hours following CGM sensor placement. BMI <45 kg/m^2. 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: Patients with a history of type 1 diabetes or late-onset autoimmune diabetes (LADA). Treatment or plan for treatment with glucocorticoids during the index hospitalization. Female patients who are pregnant (tested during hospitalization or screening) or breast-feeding during the hospitalization. Patients admitted with the following conditions: diabetic ketoacidosis, hyperosmolar hyperglycemic state, solid organ transplantation, or coronary artery bypass surgery. Prior diagnosis of gastroparesis or cirrhosis. Acute or chronic kidney disease with a serum creatinine of ≥ 2 mg/dL at the time of screening. Clinically significant nausea and/or vomiting or unable to consume more than 30 grams of carbohydrate at each meal. Patients expected to receive nothing by mouth (NPO) for >24 hours. Use of continuous or intermittent enteral feeding or parenteral nutrition. Patient receiving aspirin and/or vitamin C during the hospitalization. Any mental condition rendering the subject unable to provide informed consent. Patients currently incarcerated. Patients using >1 unit/kg/day of insulin prior to admission. Insulin pump usage within the 2 weeks prior to or during admission. Patients currently using real-time continuous glucose monitoring (CGM) or personal flash glucose monitoring system (FGM). 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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Group 1 insulin glargine and Novolog<br>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<br>* 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%<br>* Other names: Lantus®;Drug: NovoLog<br>* 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.<br>* Other names: NovoLog®;Other: Standard carbohydrate diet<br>* Standard carbohydrate diet as per usual hospital care (75g with each meal)<br>|
| Experimental: Group 2 insulin glargine and Fiasp<br>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<br>* 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%<br>* Other names: Lantus®;Drug: Insulin Fiasp<br>* 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.<br>* Other names: Fiasp®;Other: Standard carbohydrate diet<br>* Standard carbohydrate diet as per usual hospital care (75g with each meal)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glucose control | The amount of time in minutes spent in sensor glucose control target range of 100-180 mg/dL in the 4 hour postprandial period will be assessed using a continuous glucose monitoring (CGM) system. | 4 hour postprandial | 

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. | From date of admission to date of discharge, up to 30 days | 
| Percent of postprandial time 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. | 4 hour postprandial | 
| 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 | From date of admission to date of discharge, up to 30 days | 
| 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 | 
| 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. | From date of admission to date of discharge, up to 30 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. | From date of admission to date of discharge, up to 30 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fiasp, Novolog, Continuous glucose monitor (CGM), Hypoglycemia, Hyperglycemia, Hemoglobin A1c