Trial Outcomes & Findings for Comparison of Two Basal Insulin Therapies for Patients With Type 1 Diabetes (NCT NCT00487240)
NCT ID: NCT00487240
Last Updated: 2010-11-04
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
387 participants
Primary outcome timeframe
baseline and 32 weeks
Results posted on
2010-11-04
Participant Flow
First 4 weeks (Titration Period): acclimate patients to insulin regimen and optimize insulin dose. Final 28 weeks (Maintenance Period): Minimum of 6 months' stable insulin dosage. 456 patients were screened; 69 did not meet entry criteria and 387 were randomized; 6 patients were excluded from the 387 randomized to create the Full Analysis Set.
Participant milestones
| Measure |
Insulin Lispro Protamine Suspension
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
195
|
192
|
|
Overall Study
Full Analysis Set (ITT Population)
|
192
|
189
|
|
Overall Study
COMPLETED
|
164
|
166
|
|
Overall Study
NOT COMPLETED
|
31
|
26
|
Reasons for withdrawal
| Measure |
Insulin Lispro Protamine Suspension
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
12
|
6
|
|
Overall Study
Lost to Follow-up
|
7
|
6
|
|
Overall Study
Adverse Event
|
0
|
4
|
|
Overall Study
Protocol Violation
|
5
|
5
|
|
Overall Study
Entry Criteria Not Met
|
3
|
4
|
|
Overall Study
Sponsor Decision
|
2
|
1
|
|
Overall Study
Physician Decision
|
2
|
0
|
Baseline Characteristics
Comparison of Two Basal Insulin Therapies for Patients With Type 1 Diabetes
Baseline characteristics by cohort
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
Total
n=381 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
36.10 years
STANDARD_DEVIATION 13.33 • n=5 Participants
|
36.19 years
STANDARD_DEVIATION 13.09 • n=7 Participants
|
36.14 years
STANDARD_DEVIATION 13.20 • n=5 Participants
|
|
Sex: Female, Male
Female
|
96 Participants
n=5 Participants
|
91 Participants
n=7 Participants
|
187 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
96 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
194 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
34 participants
n=5 Participants
|
35 participants
n=7 Participants
|
69 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
16 participants
n=5 Participants
|
17 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
14 participants
n=5 Participants
|
12 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Greece
|
16 participants
n=5 Participants
|
16 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Argentina
|
16 participants
n=5 Participants
|
16 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
20 participants
n=5 Participants
|
19 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
22 participants
n=5 Participants
|
21 participants
n=7 Participants
|
43 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
17 participants
n=5 Participants
|
17 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
37 participants
n=5 Participants
|
36 participants
n=7 Participants
|
73 participants
n=5 Participants
|
|
Race/Ethnicity
African
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Race/Ethnicity
Caucasian
|
165 participants
n=5 Participants
|
160 participants
n=7 Participants
|
325 participants
n=5 Participants
|
|
Race/Ethnicity
East Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity
Hispanic
|
25 participants
n=5 Participants
|
28 participants
n=7 Participants
|
53 participants
n=5 Participants
|
|
Race/Ethnicity
Native American
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity
West Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Race/Ethnicity
Aboriginal and/or Torres Strait Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
25.15 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.17 • n=5 Participants
|
25.46 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.17 • n=7 Participants
|
25.30 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 4.17 • n=5 Participants
|
|
Duration of Diabetes
|
14.58 years
STANDARD_DEVIATION 10.69 • n=5 Participants
|
13.83 years
STANDARD_DEVIATION 9.80 • n=7 Participants
|
14.20 years
STANDARD_DEVIATION 10.26 • n=5 Participants
|
|
Hemoglobin A1c (HbA1c)
|
8.87 percent of HbA1c
STANDARD_DEVIATION 1.29 • n=5 Participants
|
8.64 percent of HbA1c
STANDARD_DEVIATION 1.27 • n=7 Participants
|
8.75 percent of HbA1c
STANDARD_DEVIATION 1.28 • n=5 Participants
|
PRIMARY outcome
Timeframe: baseline and 32 weeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=187 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=185 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint
Baseline
|
8.88 percent of HbA1c
Standard Error 0.10
|
8.68 percent of HbA1c
Standard Error 0.10
|
|
Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint
Change from Baseline
|
-0.69 percent of HbA1c
Standard Error 0.07
|
-0.59 percent of HbA1c
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline, 8,16, 24, 32 WeeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population.
The summary statistics represents the mean of all subjects. Change from baseline is calculated for each individual subject for the specific visit and then the "mean change from baseline" is calculated by averaging out for all subjects. \[Sum over all (i) {A1c at Week 8 for Subject(i) minus A1c Baseline for Subject (i)}/Total Subjects\]. Therefore, for example, the Change from Baseline is not equal to the difference of Mean A1c for Week 8 minus Mean A1c for baseline.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=187 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=185 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
Baseline
|
8.88 percent of HbA1c
Standard Error 0.10
|
8.68 percent of HbA1c
Standard Error 0.10
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
8 Week HbA1c (n=184, n=179)
|
8.08 percent of HbA1c
Standard Error 0.07
|
8.11 percent of HbA1c
Standard Error 0.07
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
8 Week Change from Baseline
|
-0.68 percent of HbA1c
Standard Error 0.07
|
-0.64 percent of HbA1c
Standard Error 0.07
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
16 Week HbA1c (n=174, n=173)
|
7.94 percent of HbA1c
Standard Error 0.07
|
8.08 percent of HbA1c
Standard Error 0.08
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
16 Week Change from Baseline
|
-0.81 percent of HbA1c
Standard Error 0.07
|
-0.67 percent of HbA1c
Standard Error 0.08
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
24 Week HbA1c (n=171, n=174)
|
8.07 percent of HbA1c
Standard Error 0.08
|
8.11 percent of HbA1c
Standard Error 0.08
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
24 Week Change from Baseline
|
-0.69 percent of HbA1c
Standard Error 0.08
|
-0.65 percent of HbA1c
Standard Error 0.08
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
32 Week HbA1c (n=165, n=165)
|
8.09 percent of HbA1c
Standard Error 0.08
|
8.14 percent of HbA1c
Standard Error 0.08
|
|
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Values
32 Week Change from Baseline
|
-0.68 percent of HbA1c
Standard Error 0.08
|
-0.62 percent of HbA1c
Standard Error 0.08
|
SECONDARY outcome
Timeframe: 32 WeeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=187 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=185 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c ≤7.0%
|
18.5 percentage of participants
|
18.7 percentage of participants
|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c >7.0%
|
81.5 percentage of participants
|
81.3 percentage of participants
|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c <7.0%
|
15.2 percentage of participants
|
15.4 percentage of participants
|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c ≥7.0%
|
84.8 percentage of participants
|
84.6 percentage of participants
|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c ≤6.5%
|
8.7 percentage of participants
|
9.9 percentage of participants
|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c >6.5%
|
91.3 percentage of participants
|
90.1 percentage of participants
|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c <6.5%
|
7.1 percentage of participants
|
8.2 percentage of participants
|
|
Percentage of Patients With Hemoglobin A1c (HbA1c) Less Than or Equal to 7.0% and HbA1c Less Than or Equal to 6.5%
With HbA1c ≥6.5%
|
92.9 percentage of participants
|
91.8 percentage of participants
|
SECONDARY outcome
Timeframe: 32 WeeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Actual daily mean blood glucose levels at endpoint. The SMBG excursion is the difference between the postprandial and preprandial blood glucose concentration taken at the morning, midday and evening meals.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Daily Mean 7-Point SMBG (N=164,N=172)
|
8.67 millimoles per Liter (mmol/L)
Standard Deviation 1.97
|
8.48 millimoles per Liter (mmol/L)
Standard Deviation 1.80
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Daily Mean Pre-Meal (N=174,N=181)
|
8.77 millimoles per Liter (mmol/L)
Standard Deviation 2.37
|
8.56 millimoles per Liter (mmol/L)
Standard Deviation 2.10
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Daily Mean Postprandial Meal (N=168,N=176)
|
8.70 millimoles per Liter (mmol/L)
Standard Deviation 2.08
|
8.58 millimoles per Liter (mmol/L)
Standard Deviation 2.09
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Daily Mean Morning+Evening Pre-Meal (N=174,N=181)
|
9.00 millimoles per Liter (mmol/L)
Standard Deviation 2.55
|
8.75 millimoles per Liter (mmol/L)
Standard Deviation 2.48
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Morning Pre-Meal (N=175,N=182)
|
9.09 millimoles per Liter (mmol/L)
Standard Deviation 3.18
|
8.62 millimoles per Liter (mmol/L)
Standard Deviation 3.00
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Morning Postprandial Meal (N=171,N=178)
|
8.68 millimoles per Liter (mmol/L)
Standard Deviation 2.89
|
8.56 millimoles per Liter (mmol/L)
Standard Deviation 2.73
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Midday Pre-Meal (N=175,N=181)
|
8.29 millimoles per Liter (mmol/L)
Standard Deviation 2.92
|
8.19 millimoles per Liter (mmol/L)
Standard Deviation 2.39
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Midday Postprandial Meal (N=170,N=177)
|
8.54 millimoles per Liter (mmol/L)
Standard Deviation 2.49
|
8.61 millimoles per Liter (mmol/L)
Standard Deviation 2.44
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Evening Pre-Meal (N=174,N=181)
|
8.92 millimoles per Liter (mmol/L)
Standard Deviation 2.72
|
8.87 millimoles per Liter (mmol/L)
Standard Deviation 2.90
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Evening Postprandial Meal (N=172,N=181)
|
9.05 millimoles per Liter (mmol/L)
Standard Deviation 2.97
|
8.60 millimoles per Liter (mmol/L)
Standard Deviation 2.71
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual 0300 Hours (N=167,N=173)
|
8.49 millimoles per Liter (mmol/L)
Standard Deviation 2.85
|
8.29 millimoles per Liter (mmol/L)
Standard Deviation 2.57
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Morning SMBG Excursion (N=171,N=178)
|
-0.34 millimoles per Liter (mmol/L)
Standard Deviation 2.94
|
-0.12 millimoles per Liter (mmol/L)
Standard Deviation 2.83
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Midday SMBG Excursion (N=170,N=176)
|
0.38 millimoles per Liter (mmol/L)
Standard Deviation 2.52
|
0.46 millimoles per Liter (mmol/L)
Standard Deviation 2.59
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Evening SMBG Excursion (N=172,N=181)
|
0.12 millimoles per Liter (mmol/L)
Standard Deviation 2.72
|
-0.24 millimoles per Liter (mmol/L)
Standard Deviation 3.05
|
|
7-Point Self-Monitored Blood Glucose (SMBG) at Endpoint
Actual Daily Mean SMBG Excursion (N=168,N=176)
|
0.06 millimoles per Liter (mmol/L)
Standard Deviation 1.68
|
0.01 millimoles per Liter (mmol/L)
Standard Deviation 1.71
|
SECONDARY outcome
Timeframe: 32 WeeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Glycemic variability was measured by standard deviation (SD) value of fasting blood glucose as measured by intra-patient glycemic variability (determined by the 7-point self-monitored blood glucose \[SMBG\] profiles at endpoint); mean value (M-value), which was the mean of the intra-days self-monitored blood glucose values, and by the mean of daily difference (MODD), which was the mean of the between-days self-monitored blood glucose values.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=187 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=185 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Glycemic Variability at Endpoint
Standard Deviation (SD) Value (N=172, N=180)
|
2.64 millimoles per Liter (mmol/L)
Standard Deviation 2.09
|
2.30 millimoles per Liter (mmol/L)
Standard Deviation 1.84
|
|
Glycemic Variability at Endpoint
Mean Value (M-Value) (N=175, N=182)
|
36.39 millimoles per Liter (mmol/L)
Standard Deviation 31.82
|
32.19 millimoles per Liter (mmol/L)
Standard Deviation 25.79
|
|
Glycemic Variability at Endpoint
Mean Daily Difference (MODD) Value (N=172, N=180)
|
3.04 millimoles per Liter (mmol/L)
Standard Deviation 1.90
|
2.78 millimoles per Liter (mmol/L)
Standard Deviation 1.79
|
SECONDARY outcome
Timeframe: Baseline to 32 WeeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of \<2.8 mmol/L (\<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Overall Nocturnal Episodes (N=191,N=186)
|
125 episodes of hypoglycemia
|
111 episodes of hypoglycemia
|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Endpoint Non-Nocturnal Hypoglycemic Episodes
|
127 episodes of hypoglycemia
|
129 episodes of hypoglycemia
|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Overall Non-Nocturnal Hypoglycemic Episodes
|
172 episodes of hypoglycemia
|
172 episodes of hypoglycemia
|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Endpoint Severe Hypoglycemic Episodes
|
11 episodes of hypoglycemia
|
3 episodes of hypoglycemia
|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Overall Severe Hypoglycemic Episodes (N=171,N=170)
|
24 episodes of hypoglycemia
|
13 episodes of hypoglycemia
|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Overall Hypoglycemic Episodes
|
173 episodes of hypoglycemia
|
173 episodes of hypoglycemia
|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Endpoint Nocturnal Hypoglycemic Episodes
|
69 episodes of hypoglycemia
|
55 episodes of hypoglycemia
|
|
Number of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe Hypoglycemia) Overall and at Endpoint
Endpoint Hypoglycemic Episodes
|
134 episodes of hypoglycemia
|
135 episodes of hypoglycemia
|
SECONDARY outcome
Timeframe: baseline to 32 weeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Nocturnal: Defined as any hypoglycemic event that occurs between bedtime and waking. Non-Nocturnal: Defined as any hypoglycemic event that occurs between waking and bedtime. Severe: An episode with symptoms consistent with neuroglycopenia in which the patient requires the assistance of another person; associated with either a blood glucose level of \<2.8 mmol/L (\<50 mg/dL) or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Hypoglycemic Rate
|
76.45 hypoglycemic events per 1 year
Standard Deviation 85.07
|
61.21 hypoglycemic events per 1 year
Standard Deviation 64.25
|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Non-Nocturnal Hypoglycemic Rate
|
57.08 hypoglycemic events per 1 year
Standard Deviation 83.17
|
46.88 hypoglycemic events per 1 year
Standard Deviation 65.28
|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Non-Nocturnal Hypoglycemic Rate
|
66.58 hypoglycemic events per 1 year
Standard Deviation 78.63
|
54.83 hypoglycemic events per 1 year
Standard Deviation 58.94
|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Severe Hypoglycemic Rate
|
0.63 hypoglycemic events per 1 year
Standard Deviation 3.08
|
0.10 hypoglycemic events per 1 year
Standard Deviation 0.79
|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Severe Hypoglycemic Rate
|
0.42 hypoglycemic events per 1 year
Standard Deviation 1.43
|
0.25 hypoglycemic events per 1 year
Standard Deviation 1.26
|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Hypoglycemic Rate
|
66.41 hypoglycemic events per 1 year
Standard Deviation 90.91
|
52.60 hypoglycemic events per 1 year
Standard Deviation 70.62
|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Nocturnal Hypoglcemic Rate
|
8.90 hypoglycemic events per 1 year
Standard Deviation 18.65
|
5.60 hypoglycemic events per 1 year
Standard Deviation 13.20
|
|
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Nocturnal Hypoglycemic Rate
|
9.65 hypoglycemic events per 1 year
Standard Deviation 15.01
|
6.01 hypoglycemic events per 1 year
Standard Deviation 10.31
|
SECONDARY outcome
Timeframe: baseline to 32 weeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Hypogylcemic Rate
|
5.45 hypoglycemic events per 30 days
Standard Deviation 7.47
|
4.32 hypoglycemic events per 30 days
Standard Deviation 5.80
|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Hypoglycemic Rate
|
6.28 hypoglycemic events per 30 days
Standard Deviation 6.99
|
5.03 hypoglycemic events per 30 days
Standard Deviation 5.28
|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Nocturnal Hypoglycemic Rate
|
0.73 hypoglycemic events per 30 days
Standard Deviation 1.53
|
0.46 hypoglycemic events per 30 days
Standard Deviation 1.08
|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Nocturnal Hypoglycemic Rate
|
0.79 hypoglycemic events per 30 days
Standard Deviation 1.23
|
0.49 hypoglycemic events per 30 days
Standard Deviation 0.85
|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Non-Nocturnal Hypoglycemic Rate
|
4.69 hypoglycemic events per 30 days
Standard Deviation 6.83
|
3.85 hypoglycemic events per 30 days
Standard Deviation 5.36
|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Non-Nocturnal Hypoglycemic Rate
|
5.47 hypoglycemic events per 30 days
Standard Deviation 6.46
|
4.50 hypoglycemic events per 30 days
Standard Deviation 4.84
|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Endpoint Severe Hypoglycemic Rate
|
0.05 hypoglycemic events per 30 days
Standard Deviation 0.25
|
0.01 hypoglycemic events per 30 days
Standard Deviation 0.06
|
|
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal, Non-Nocturnal, and Severe) Overall and at Endpoint
Overall Severe Hypoglycemic Rate
|
0.03 hypoglycemic events per 30 days
Standard Deviation 0.12
|
0.02 hypoglycemic events per 30 days
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: Baseline, 32 WeeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Change From Baseline in Absolute Body Weight at 32 Week Endpoint
Baseline
|
72.76 kilograms
Standard Deviation 15.53
|
72.69 kilograms
Standard Deviation 14.59
|
|
Change From Baseline in Absolute Body Weight at 32 Week Endpoint
Change from Baseline
|
1.54 kilograms
Standard Deviation 3.18
|
0.58 kilograms
Standard Deviation 3.19
|
SECONDARY outcome
Timeframe: 32 WeeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Total daily insulin dose adjusted for body weight (U/kg/day) was assessed.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Insulin Dose Per Body Weight (Total and By Component [Basal and Bolus])
Total Basal Insulin (N=192, N=188)
|
0.53 units of insulin per kilogram per day
Standard Deviation 0.20
|
0.55 units of insulin per kilogram per day
Standard Deviation 0.26
|
|
Insulin Dose Per Body Weight (Total and By Component [Basal and Bolus])
Total Insulin (N=192, N=188)
|
0.91 units of insulin per kilogram per day
Standard Deviation 0.30
|
0.99 units of insulin per kilogram per day
Standard Deviation 0.41
|
|
Insulin Dose Per Body Weight (Total and By Component [Basal and Bolus])
Total Bolus Insulin (N=191, N=187)
|
0.39 units of insulin per kilogram per day
Standard Deviation 0.17
|
0.45 units of insulin per kilogram per day
Standard Deviation 0.22
|
SECONDARY outcome
Timeframe: 32 weeksPopulation: Number of randomized patients with baseline and at least one post-baseline value. Intent to treat population. Last observation carried forward.
Total daily insulin dose (U/day) was assessed.
Outcome measures
| Measure |
Insulin Lispro Protamine Suspension
n=192 Participants
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
n=189 Participants
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Insulin Dose (Total and By Component [Basal and Bolus])
Total Insulin (N=192, N=188)
|
67.78 units of insulin per day (U/day)
Standard Deviation 27.42
|
73.84 units of insulin per day (U/day)
Standard Deviation 38.38
|
|
Insulin Dose (Total and By Component [Basal and Bolus])
Total Bolus Insulin (N=191, N=187)
|
28.94 units of insulin per day (U/day)
Standard Deviation 14.69
|
33.32 units of insulin per day (U/day)
Standard Deviation 20.41
|
|
Insulin Dose (Total and By Component [Basal and Bolus])
Total Basal Insulin (N=192, N=188)
|
38.99 units of insulin per day (U/day)
Standard Deviation 17.37
|
40.70 units of insulin per day (U/day)
Standard Deviation 22.29
|
Adverse Events
Insulin Lispro Protamine Suspension
Serious events: 10 serious events
Other events: 93 other events
Deaths: 0 deaths
Detemir
Serious events: 3 serious events
Other events: 86 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Insulin Lispro Protamine Suspension
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Endocrine disorders
Autoimmune thyroiditis
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Endocrine disorders
Hyperthyroidism
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Gastrointestinal disorders
Abdominal pain
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Gastrointestinal disorders
Mouth cyst
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
General disorders
Chest pain
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Infections and infestations
Cellulitis
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/192
|
0.53%
1/189 • Number of events 1
|
|
Infections and infestations
Respiratory tract infection
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Metabolism and nutrition disorders
Diabetic foot
|
0.00%
0/192
|
0.53%
1/189 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.52%
1/192 • Number of events 2
|
0.00%
0/189
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.52%
1/192 • Number of events 1
|
0.53%
1/189 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Nervous system disorders
Diabetic neuropathy
|
0.00%
0/192
|
0.53%
1/189 • Number of events 1
|
|
Nervous system disorders
Hypoglycaemic coma
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.52%
1/192 • Number of events 1
|
0.00%
0/189
|
Other adverse events
| Measure |
Insulin Lispro Protamine Suspension
Patient specific dose insulin lispro protamine suspension, twice daily (BID), within 15 minutes before meals, subcutaneous (SC) injection x 32 weeks
|
Detemir
Patient specific dose insulin Levemir (detemir) twice daily (BID) subcutaneous (SC) injection x 32 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.6%
3/192 • Number of events 4
|
3.7%
7/189 • Number of events 8
|
|
Gastrointestinal disorders
Nausea
|
3.1%
6/192 • Number of events 7
|
2.6%
5/189 • Number of events 8
|
|
Gastrointestinal disorders
Toothache
|
0.52%
1/192 • Number of events 2
|
2.6%
5/189 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
5/192 • Number of events 6
|
1.1%
2/189 • Number of events 2
|
|
General disorders
Fatigue
|
1.0%
2/192 • Number of events 2
|
2.1%
4/189 • Number of events 7
|
|
General disorders
Pyrexia
|
2.1%
4/192 • Number of events 5
|
0.00%
0/189
|
|
Infections and infestations
Gastroenteritis
|
2.6%
5/192 • Number of events 5
|
1.6%
3/189 • Number of events 4
|
|
Infections and infestations
Influenza
|
7.8%
15/192 • Number of events 16
|
8.5%
16/189 • Number of events 18
|
|
Infections and infestations
Nasopharyngitis
|
14.1%
27/192 • Number of events 30
|
9.5%
18/189 • Number of events 24
|
|
Infections and infestations
Pharyngitis
|
3.1%
6/192 • Number of events 6
|
2.1%
4/189 • Number of events 4
|
|
Infections and infestations
Sinusitis
|
3.6%
7/192 • Number of events 7
|
3.7%
7/189 • Number of events 7
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/192
|
3.2%
6/189 • Number of events 6
|
|
Infections and infestations
Urinary tract infection
|
1.6%
3/192 • Number of events 3
|
2.1%
4/189 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/192
|
2.6%
5/189 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.0%
2/192 • Number of events 3
|
2.1%
4/189 • Number of events 5
|
|
Nervous system disorders
Headache
|
9.4%
18/192 • Number of events 32
|
7.4%
14/189 • Number of events 35
|
|
Nervous system disorders
Migraine
|
2.6%
5/192 • Number of events 5
|
0.53%
1/189 • Number of events 2
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
2.1%
4/192 • Number of events 16
|
1.6%
3/189 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.1%
6/192 • Number of events 8
|
5.3%
10/189 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
2.6%
5/192 • Number of events 5
|
2.6%
5/189 • Number of events 18
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60