Type 2 Diabetes Treated With Insulin
Conditions
Keywords
Fiasp, Novolog, Continuous glucose monitor (CGM), Hypoglycemia, Hyperglycemia, Hemoglobin A1c
Brief summary
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.
Interventions
DRUGInsulin 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%
DRUGNovoLog
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.
DRUGInsulin 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.
Standard carbohydrate diet as per usual hospital care (75g with each meal)
Sponsors
Novo Nordisk A/S
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial Glucose Control | 3 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Time Spent in Glycemic Range of 70-140 mg/dL | 3 days | 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. |
| Percent of Time Spent With Hypoglycemia During Hospitalization | 3 days | 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. |
| Percent of Nocturnal Time in Glycemic Target Range 100-180 mg/dL | 3 days | The percent of nocturnal time (from 00.01 AM to 5:59 AM) in the glycemic target range of 100-180 mg/dL |
| Glycemic Control While Hospitalized | 3 days | 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. |
| Percent of Postprandial Time Spent With Level 1 Hyperglycemia | 4 hours postprandial | The percent of time spent in level 1 hyperglycemia (181-239 mg/dL) will be assessed using CGM in the 4 hour postprandial period. |
| Percent of Postprandial Time Spent With Level 2 Hyperglycemia | 4 hours postprandial | The percent of time spent in level 2 hyperglycemia (\>240 mg/dL) will be assessed using CGM in the 4 hour postprandial period. |
| Percent of Postprandial Time Spent With Hypoglycemia | 4 hours postprandial | The percent of postprandial time in three categories of hypoglycemia will be assessed: \<70 mg/dL, \<54 mg/dL, and \<40 mg/dL. |
| Percent of Nocturnal Time Spent With Hypoglycemia | 3 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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%
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.
Standard carbohydrate diet: Standard carbohydrate diet as per usual hospital care (75g with each meal) | 68 |
| 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.
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%
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.
Standard carbohydrate diet: Standard carbohydrate diet as per usual hospital care (75g with each meal) | 69 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed at Least 4 Meals | Bleeding at CGM site | 0 | 1 |
| Completed at Least 4 Meals | Early discharge | 5 | 5 |
| Completed at Least 4 Meals | Nutrition method changed | 1 | 0 |
| Completed at Least 4 Meals | Started oral antihyperglycemic | 1 | 1 |
| Completed at Least 4 Meals | Transfer to ICU | 0 | 1 |
| Insulin Boluses & Postprandial CGM Data | Postprandial or CGM data not available | 5 | 12 |
Baseline characteristics
| Characteristic | Total | Group 2 Insulin Glargine and Fiasp | Group 1 Insulin Glargine and Novolog |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 11.1 | 59.4 years STANDARD_DEVIATION 10.1 | 57.2 years STANDARD_DEVIATION 12 |
| Diabetes treatment prior to admission Insulin use | 88 Participants | 43 Participants | 45 Participants |
| Diabetes treatment prior to admission Non-insulin injectable agents | 43 Participants | 22 Participants | 21 Participants |
| Diabetes treatment prior to admission Oral agents | 93 Participants | 48 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 20 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 94 Participants | 49 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 68 Participants | 33 Participants | 35 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 27 Participants | 16 Participants | 11 Participants |
| Race (NIH/OMB) White | 41 Participants | 20 Participants | 21 Participants |
| Region of Enrollment United States | 137 participants | 69 participants | 68 participants |
| Sex: Female, Male Female | 46 Participants | 22 Participants | 24 Participants |
| Sex: Female, Male Male | 91 Participants | 47 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 61 |
| other Total, other adverse events | 0 / 61 | 1 / 61 |
| serious Total, serious adverse events | 0 / 61 | 1 / 61 |
Outcome results
Primary
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.
Time frame: 3 days
Population: A total of 110 participants received at least 4 meal boluses and had adequate 4-hr CG data for analysis. Results presented as percentage time in range 100-180 mg/dL in the 4 hour postprandial period for each group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Postprandial Glucose Control | 36.18 percentage of time in range (TIR) | Standard Deviation 29.78 |
| Group 2 Insulin Glargine and Fiasp | Postprandial Glucose Control | 45.22 percentage of time in range (TIR) | Standard Deviation 32.63 |
Secondary
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.
Time frame: 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Glycemic Control While Hospitalized | 34.9 percentage of time in range (TIR) | Standard Deviation 26 |
| Group 2 Insulin Glargine and Fiasp | Glycemic Control While Hospitalized | 39.9 percentage of time in range (TIR) | Standard Deviation 26.6 |
Secondary
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
Time frame: 3 days
Population: Only participants with 95% valid CGM data were included in this overnight analysis. This was a total of 108 participants- 56 in the Novolog group and 52 in the Fiasp group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Percent of Nocturnal Time in Glycemic Target Range 100-180 mg/dL | 36.7 percentage of time in range (TIR) | Standard Deviation 37.4 |
| Group 2 Insulin Glargine and Fiasp | Percent of Nocturnal Time in Glycemic Target Range 100-180 mg/dL | 42.1 percentage of time in range (TIR) | Standard Deviation 40.7 |
Secondary
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.
Time frame: 3 days
Population: Patients with adequate overnight CGM data for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Percent of Nocturnal Time Spent With Hypoglycemia | <70 mg/dL | 0.52 percent time in range | Standard Deviation 2.44 |
| Group 1 Insulin Glargine and Novolog | Percent of Nocturnal Time Spent With Hypoglycemia | <54 mg/dL | 0.043 percent time in range | Standard Deviation 0.24 |
| Group 1 Insulin Glargine and Novolog | Percent of Nocturnal Time Spent With Hypoglycemia | <40 | 0 percent time in range | Standard Deviation 0 |
| Group 2 Insulin Glargine and Fiasp | Percent of Nocturnal Time Spent With Hypoglycemia | <70 mg/dL | 1.12 percent time in range | Standard Deviation 4.85 |
| Group 2 Insulin Glargine and Fiasp | Percent of Nocturnal Time Spent With Hypoglycemia | <54 mg/dL | 0.22 percent time in range | Standard Deviation 1.31 |
| Group 2 Insulin Glargine and Fiasp | Percent of Nocturnal Time Spent With Hypoglycemia | <40 | 0.073 percent time in range | Standard Deviation 0.56 |
Secondary
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.
Time frame: 4 hours postprandial
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Percent of Postprandial Time Spent With Hypoglycemia | BG <70 mg/dL | 0.70 percentage of time in range (TIR) | Standard Deviation 2.32 |
| Group 1 Insulin Glargine and Novolog | Percent of Postprandial Time Spent With Hypoglycemia | BG <54 mg/dL | 0.14 percentage of time in range (TIR) | Standard Deviation 0.85 |
| Group 1 Insulin Glargine and Novolog | Percent of Postprandial Time Spent With Hypoglycemia | BG <40 mg/dL | 0.01 percentage of time in range (TIR) | Standard Deviation 0.07 |
| Group 2 Insulin Glargine and Fiasp | Percent of Postprandial Time Spent With Hypoglycemia | BG <70 mg/dL | 0.76 percentage of time in range (TIR) | Standard Deviation 3.37 |
| Group 2 Insulin Glargine and Fiasp | Percent of Postprandial Time Spent With Hypoglycemia | BG <54 mg/dL | 012 percentage of time in range (TIR) | Standard Deviation 0.75 |
| Group 2 Insulin Glargine and Fiasp | Percent of Postprandial Time Spent With Hypoglycemia | BG <40 mg/dL | 0.03 percentage of time in range (TIR) | Standard Deviation 0.19 |
Secondary
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.
Time frame: 4 hours postprandial
Population: There were 110 participants (57 in the Novolog arm and 53 in the Fiasp arm) with 4-hour postprandial data available for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Percent of Postprandial Time Spent With Level 1 Hyperglycemia | 30.1 percentage of time in range (TIR) | Standard Deviation 16.9 |
| Group 2 Insulin Glargine and Fiasp | Percent of Postprandial Time Spent With Level 1 Hyperglycemia | 23.3 percentage of time in range (TIR) | Standard Deviation 19.2 |
Secondary
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.
Time frame: 4 hours postprandial
Population: There were 110 participants (57 in the Novolog arm and 53 in the Fiasp arm) with 4-hour postprandial data available for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Percent of Postprandial Time Spent With Level 2 Hyperglycemia | 30.3 percentage of time in range (TIR) | Standard Deviation 31.2 |
| Group 2 Insulin Glargine and Fiasp | Percent of Postprandial Time Spent With Level 2 Hyperglycemia | 26.7 percentage of time in range (TIR) | Standard Deviation 31.2 |
Secondary
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.
Time frame: 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Percent of Time Spent in Glycemic Range of 70-140 mg/dL | 16.9 percentage of time in range (TIR) | Standard Deviation 18.4 |
| Group 2 Insulin Glargine and Fiasp | Percent of Time Spent in Glycemic Range of 70-140 mg/dL | 20.2 percentage of time in range (TIR) | Standard Deviation 21.3 |
Secondary
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.
Time frame: 3 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1 Insulin Glargine and Novolog | Percent of Time Spent With Hypoglycemia During Hospitalization | BG <70 dL/mg | 0.80 percentage of time in range (TIR) | Standard Deviation 2.1 |
| Group 1 Insulin Glargine and Novolog | Percent of Time Spent With Hypoglycemia During Hospitalization | BG <54 dL/mg | 0.16 percentage of time in range (TIR) | Standard Deviation 0.6 |
| Group 1 Insulin Glargine and Novolog | Percent of Time Spent With Hypoglycemia During Hospitalization | BG <40 dL/mg | 0.02 percentage of time in range (TIR) | Standard Deviation 0.08 |
| Group 2 Insulin Glargine and Fiasp | Percent of Time Spent With Hypoglycemia During Hospitalization | BG <70 dL/mg | 1.52 percentage of time in range (TIR) | Standard Deviation 4.6 |
| Group 2 Insulin Glargine and Fiasp | Percent of Time Spent With Hypoglycemia During Hospitalization | BG <54 dL/mg | 0.53 percentage of time in range (TIR) | Standard Deviation 1.7 |
| Group 2 Insulin Glargine and Fiasp | Percent of Time Spent With Hypoglycemia During Hospitalization | BG <40 dL/mg | 0.10 percentage of time in range (TIR) | Standard Deviation 0.44 |