Renal Insufficiency, Type 2 Diabetes
Conditions
Keywords
glargine, glulisine, type 2 diabetes, renal insufficiency
Brief summary
It is imperative to devise easy to follow, yet appropriate, guidelines for insulin use in renal-impaired patients. This will be done by comparing two regimens: 1) glargine once daily plus mealtime glulisine based on weight alone and 2) a predetermined dosing reduction algorithm with glargine/glulisine based on weight with reduction for decreased estimated GFR by MDRD as follows: \< 30 ml/min/1.73m2 or on dialysis reduce dose by 50% from weight based calculation.
Detailed description
This study will enroll 180 hospitalized patients with Type 2 diabetes and moderate to end stage renal insufficiency (estimated glomerular filtration rate is \< 30 ml/min/1.73m2 or dialysis) in the Chicagoland area. Participants will be randomized into 1 of 2 protocols after hospital admission. Blood glucose levels will be obtained before meals, at bedtime and whenever necessary for any signs or symptoms of hypoglycemia. The primary endpoint will be the percentage of blood glucose levels reaching goal of 80-180mg/dl. A secondary endpoint will be the percentage of hypoglycemic events, defined as blood glucose values \< 60 mg/dl. In addition the percentage of glucose levels within the goal range of 80-180mg.dl will be further separated into excellent control (80-140mg/dl) and acceptable control (141-180mg/dl). The 2 study groups will be: 1. Glargine & glulisine. The total daily insulin dose will be 0.6 units/kg. Half of this will be given as glargine once daily. The other half will be given as glulisine, divided equally between breakfast, lunch, and dinner with correction factor dosing as needed for elevated premeal hyperglycemia. 2. Glargine & glulisine The calculation for the total daily insulin dose will be 0.3 units/kg. Half of this will be given as glargine in the morning. The other half will be given as glulisine, divided equally between breakfast, lunch, and dinner, with correction factor dosing as needed for elevated premeal hyperglycemia. All oral agents will be discontinued on admission.
Interventions
DRUG0.5 units/kg daily insulin
Participants randomized to receive this intervention will receive a standard-dose of 0.5 units/kg daily insulin. Half of this dose will be given as glargine and the other half will be given as glulisine.
DRUG0.25 units/kg daily insulin
Participants randomized to receive this intervention will receive an experimental dose of 0.25 units/kg daily insulin. Half of this dose will be given as glargine and the other half will be given as glulisine.
Sponsors
Sanofi
Loyola University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible participants are randomized to one of the two dosing groups using a 1:1 allocation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 Diabetes Mellitus of mor than 1year * GFR less than 30 ml/min/1.73m2 or dialysis * Age greater than 18years * Entry blood glucose (fasting or random) greater than 180mg%
Exclusion criteria
* Type 1 Diabetes Mellitus * New onset hyperglycemia * Pregnant * Solid organ transplant within 1 year * Steroids prednisone greater than 7.5mg/day or equivalent * Hospital LOS predicted less than 2 days * Severe liver disease * Known hypopituitarism or adrenal insufficiency * Patients in the ICU * Patients with hypoglycemic unawareness * Outpatient insulin dose less than 0.6 units/kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Blood Glucose Over 6 Days | 6 Days | Participants have their blood glucose measured daily for six days. The average blood glucose measure over all six days is compared between the two treatment cohorts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Experience at Least One Blood Glucose Level Below 70 Milligrams Per Deciliter | 6 Days | At the end of the study, the number of participants who experience at least one blood glucose level below 70 milligrams per deciliter (mg/dL) is compared between the two treatment cohorts |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study took place at Loyola University Medical Center (Maywood, IL), Rush University Medical Center (Chicago, IL), and Northwestern University Medical Center (Chicago, IL) between January 2009 and May 2011
Participants by arm
| Arm | Count |
|---|---|
| 0.5 Units/kg Participants randomized to this arm will receive a standard-dose of 0.5 units/kg daily insulin. Half of this dose will be given as glargine and the other half will be given as glulisine.
0.5 units/kg daily insulin: Participants randomized to receive this intervention will receive a standard-dose of 0.5 units/kg daily insulin. Half of this dose will be given as glargine and the other half will be given as glulisine. | 50 |
| 0.25 Units/kg Participants randomized to this arm will receive an experimental dose of 0.25 units/kg daily insulin. Half of this dose will be given as glargine and the other half will be given as glulisine.
0.25 units/kg daily insulin: Participants randomized to receive this intervention will receive an experimental dose of 0.25 units/kg daily insulin. Half of this dose will be given as glargine and the other half will be given as glulisine. | 57 |
| Total | 107 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 0 |
Baseline characteristics
| Characteristic | Total | 0.25 Units/kg | 0.5 Units/kg |
|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 11 | 63.7 years STANDARD_DEVIATION 13 | 65.3 years STANDARD_DEVIATION 10.6 |
| Glomerular filtration rate | 29.9 mL/min/1.73 squared meters STANDARD_DEVIATION 9 | 29.6 mL/min/1.73 squared meters STANDARD_DEVIATION 10 | 30.4 mL/min/1.73 squared meters STANDARD_DEVIATION 8.3 |
| Glycated hemoglobin | 8.0 Percentage (%) STANDARD_DEVIATION 2 | 7.9 Percentage (%) STANDARD_DEVIATION 1.9 | 8.2 Percentage (%) STANDARD_DEVIATION 2.1 |
| Insulin therapy before admission Insulin before admission | 81 Participants | 42 Participants | 39 Participants |
| Insulin therapy before admission No insulin before admission | 26 Participants | 15 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 22 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 32 Participants | 32 Participants |
| Sex: Female, Male Female | 58 Participants | 28 Participants | 30 Participants |
| Sex: Female, Male Male | 49 Participants | 29 Participants | 20 Participants |
| Total home daily insulin dose | 52.0 units of insulin STANDARD_DEVIATION 43 | 51.6 units of insulin STANDARD_DEVIATION 46.3 | 54.3 units of insulin STANDARD_DEVIATION 40.7 |
| Years of Diabetes | 17.6 years STANDARD_DEVIATION 10 | 16.6 years STANDARD_DEVIATION 9.9 | 18.6 years STANDARD_DEVIATION 8.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 0 / 57 | 0 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 |
Outcome results
Primary
Average Blood Glucose Over 6 Days
Participants have their blood glucose measured daily for six days. The average blood glucose measure over all six days is compared between the two treatment cohorts.
Time frame: 6 Days
Population: The analysis population for the primary outcome comprises all participants who were randomized and completed all study activities
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.5 Units/kg | Average Blood Glucose Over 6 Days | 174 milligrams per deciliter | Standard Deviation 52.3 |
| 0.25 Units/kg | Average Blood Glucose Over 6 Days | 174.5 milligrams per deciliter | Standard Deviation 46 |
Comparison: The null hypothesis is that there is no difference between the two treatment cohorts on their average blood glucose levelp-value: 0.95895% CI: [-19.341, 18.341]t-test, 2 sided
Secondary
The Number of Participants Who Experience at Least One Blood Glucose Level Below 70 Milligrams Per Deciliter
At the end of the study, the number of participants who experience at least one blood glucose level below 70 milligrams per deciliter (mg/dL) is compared between the two treatment cohorts
Time frame: 6 Days
Population: This analysis comprises all participants who were randomized and completed all study activities
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.5 Units/kg | The Number of Participants Who Experience at Least One Blood Glucose Level Below 70 Milligrams Per Deciliter | At least one blood glucose level below 70 mg/dL | 15 Participants |
| 0.5 Units/kg | The Number of Participants Who Experience at Least One Blood Glucose Level Below 70 Milligrams Per Deciliter | No blood glucose level below 70 mg/dL | 35 Participants |
| 0.25 Units/kg | The Number of Participants Who Experience at Least One Blood Glucose Level Below 70 Milligrams Per Deciliter | No blood glucose level below 70 mg/dL | 48 Participants |
| 0.25 Units/kg | The Number of Participants Who Experience at Least One Blood Glucose Level Below 70 Milligrams Per Deciliter | At least one blood glucose level below 70 mg/dL | 9 Participants |
Comparison: The null hypothesis is that there is no difference in the odds of experiencing at least one blood glucose level below 70 mg/dL between the two treatment cohorts.p-value: 0.082895% CI: [0.172, 1.114]Regression, Logistic