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Comparison of Two Basal Insulins for Patients With Type 2 Diabetes on Anti-Hyperglycemic Medications (IOPE) (IOPE)

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ClinicalTrials.gov Identifier: NCT00510952
Recruitment Status : Completed
First Posted : August 3, 2007
Results First Posted : November 3, 2009
Last Update Posted : October 21, 2010
Sponsor:
Information provided by:
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Interventions Drug: Insulin Lispro Protamine Suspension
Drug: Insulin Glargine
Enrollment 471
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lispro Glargine
Hide Arm/Group Description Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Period Title: Overall Study
Started 235 236
Full Analysis Set (Intent to Treat) 229 229
Completed 209 220
Not Completed 26 16
Reason Not Completed
Adverse Event             1             0
Entry Criteria Not Met             3             1
Lost to Follow-up             5             3
Physician Decision             1             1
Protocol Violation             7             4
Sponsor Decision             1             0
Withdrawal by Subject             6             7
Did Not Receive Study Drug             2             0
Arm/Group Title Lispro Glargine Total
Hide Arm/Group Description Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks Total of all reporting groups
Overall Number of Baseline Participants 229 229 458
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 229 participants 229 participants 458 participants
58.05  (9.35) 57.29  (8.99) 57.67  (9.17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 229 participants 229 participants 458 participants
Female
107
  46.7%
116
  50.7%
223
  48.7%
Male
122
  53.3%
113
  49.3%
235
  51.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 229 participants 229 participants 458 participants
Argentina 13 12 25
Brazil 18 19 37
Canada 20 20 40
India 27 31 58
Korea, Republic of 9 13 22
Mexico 18 16 34
Poland 52 50 102
Russian Federation 30 29 59
Spain 9 10 19
United States 33 29 62
Race/Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 229 participants 229 participants 458 participants
African 11 14 25
Caucasian 147 142 289
East Asian 10 15 25
Hispanic 33 26 59
Native American 0 1 1
West Asian (Indian sub-continent) 28 31 59
Sulfonylurea Group   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 229 participants 229 participants 458 participants
Yes 191 190 381
No 38 39 77
[1]
Measure Description: Patients with previous sulfonylurea use.
Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kilograms per square meter (kg/m^2)
Number Analyzed 229 participants 229 participants 458 participants
30.69  (5.01) 31.62  (5.48) 31.16  (5.27)
[1]
Measure Description: Body mass index is an estimate of body fat based on body weight divided by height squared.
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)
Number Analyzed 229 participants 229 participants 458 participants
84.23  (16.83) 86.05  (18.62) 85.14  (17.75)
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 229 participants 229 participants 458 participants
9.80  (6.45) 9.90  (6.51) 9.85  (6.47)
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters (cm)
Number Analyzed 229 participants 229 participants 458 participants
165.45  (10.04) 164.62  (10.11) 165.03  (10.07)
1.Primary Outcome
Title Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c)
Hide Description [Not Specified]
Time Frame Baseline, 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement. Last observation carried forward.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 225 226
Least Squares Mean (Standard Error)
Unit of Measure: percent of HbA1c
Baseline 8.70  (0.06) 8.69  (0.06)
Change from Baseline -1.46  (0.07) -1.41  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments Hypothesis: Basal analog insulin lispro protamine suspension, injected once or twice daily is noninferior to basal analog insulin glargine, injected once a day, with regard to glycemic control as measured by change in HbA1c from baseline to 24 week endpoint (last observation carried forward).
Type of Statistical Test Non-Inferiority or Equivalence
Comments Noninferiority margin was 0.4%.
Statistical Test of Hypothesis P-Value 0.551
Comments P-value for Change from Baseline.
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.05
Confidence Interval 95%
-0.21 to 0.11
Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Glargine).
2.Secondary Outcome
Title Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value
Hide Description [Not Specified]
Time Frame Baseline, 12 Weeks, 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 229 229
Least Squares Mean (Standard Error)
Unit of Measure: percent hemoglobin
Baseline (n= 225, n= 226) 8.70  (0.06) 8.69  (0.06)
Week 12 HbA1c (n=213, n=220) 7.30  (0.07) 7.36  (0.07)
Week 12 Change from Baseline (n=213, n=220) -1.36  (0.07) -1.30  (0.07)
Week 24 HbA1c (n=206, n=218) 7.15  (0.07) 7.24  (0.07)
Week 24 Change from Baseline (n=206, n=218) -1.52  (0.07) -1.43  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments P-value for Week 12 HbA1c.
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.06
Confidence Interval 95%
-0.21 to 0.09
Estimation Comments The two-sides 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Glargine).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments P-value for Week 12 Change from Baseline.
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.06
Confidence Interval 95%
-0.21 to 0.09
Estimation Comments The two-sides 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Glargine).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.254
Comments P-value for Week 24 HbA1c.
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.09
Confidence Interval 95%
-0.25 to 0.07
Estimation Comments The two-sides 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Glargine).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.254
Comments P-value for Week 24 Change from Baseline.
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline Sulfonylurea Group.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.09
Confidence Interval 95%
-0.25 to 0.07
Estimation Comments The two-sides 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Glargine).
3.Secondary Outcome
Title Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint
Hide Description Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7% and less than or equal to 6.5% at endpoint.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement. Last observation carried forward.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 226 226
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c <7.0% 43.8 41.2
HbA1c ≤6.5% 24.8 21.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.634
Comments P-value for HbA1c <7.0%.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.504
Comments P-value for HbA1c ≤6.5%.
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Glycemic Variability at Endpoint
Hide Description 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-monitoring blood glucose (SMBG) profiles at endpoint) based on the actual morning pre-meal blood glucose.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement. Last observation carried forward.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 228 229
Mean (Standard Deviation)
Unit of Measure: millimoles per liter (mmol/L)
1.01  (0.72) 0.94  (0.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments Hypothesis: Insulin lispro protamine suspension is noninferior to glargine at actual morning pre-meal at endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Noninferiority margin of 0.8 millimoles per liter (mmol/L).
Statistical Test of Hypothesis P-Value 0.323
Comments [Not Specified]
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.06
Confidence Interval 95%
-0.06 to 0.19
Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatment groups (Insulin Lispro Protamine Suspension minus Glargine).
5.Secondary Outcome
Title 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint
Hide Description Actual measurements and daily mean blood glucose levels at endpoint.
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement. Last observation carried forward.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 226 226
Mean (Standard Deviation)
Unit of Measure: millimoles per liter (mmol/L)
Actual Morning Pre-Meal 6.47  (1.40) 6.33  (1.36)
Actual Morning Postprandial Meal 8.64  (2.48) 9.00  (2.55)
Actual Midday Pre-Meal 6.93  (2.11) 7.16  (2.07)
Actual Midday Postprandial Meal 9.09  (2.52) 9.17  (2.50)
Actual Evening Pre-Meal 7.50  (2.06) 7.54  (2.02)
Actual Evening Postprandial Meal 9.19  (2.84) 9.29  (2.54)
Actual 0300 Hours 6.79  (2.05) 7.00  (2.21)
Daily Mean 7-Point SMBG 7.79  (1.82) 7.96  (1.74)
Daily Mean Pre-Meal 6.99  (1.77) 7.04  (1.55)
Daily Mean Postprandial Meal 8.96  (2.25) 9.18  (2.20)
Daily Mean Morning+Evening Pre-Meal 6.99  (1.51) 6.93  (1.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.302
Comments P-value for Actual Morning Pre-Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.144
Comments P-value for Actual Morning Postprandial Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.279
Comments P-value for Actual Midday Pre-Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.928
Comments P-value for Actual Midday Postprandial Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.918
Comments P-value for Actual Evening Pre-Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.875
Comments P-value for Actual Evening Postprandial Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.316
Comments P-value for Actual 0300 Hours.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.389
Comments P-value for Daily Mean 7-Point SMBG.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.836
Comments P-value for Daily Mean Pre-Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.394
Comments P-value for Daily Mean Postprandial Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.609
Comments P-value for Daily Mean Morning+Evening Pre-Meal.
Method ANOVA
Comments ANOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
6.Secondary Outcome
Title Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall
Hide Description Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe Hypoglycemia: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with either a Roche blood glucose value <2.8 millimoles/liter or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 229 229
Measure Type: Number
Unit of Measure: participants
All Hypoglycemic Episodes 168 160
Nocturnal Hypoglycemic Episodes 114 87
Severe Hypoglycemic Episodes 9 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.468
Comments P-value for All Hypoglycemic Episodes.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments P-value for Nocturnal Hypoglycemic Episodes.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments P-value for Severe Hypoglycemic Episodes.
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall
Hide Description Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 1-year adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 365.25 days.
Time Frame Baseline to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 229 229
Mean (Standard Deviation)
Unit of Measure: hypoglycemic event per 1 year
Hypoglycemic Rate 24.16  (28.78) 22.95  (30.87)
Nocturnal Hypoglycemic Rate 6.08  (10.62) 4.08  (9.40)
Severe Hypoglycemic Rate 0.11  (0.58) 0.02  (0.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.316
Comments P-value for Hypoglycemic Rate.
Method ANOVA
Comments Nonparametric ANOVA Model: Rank of Variable=Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group. Hypoglycemic Rate (1 year) was used.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments P-Value for Nocturnal Hypoglycemic Rate.
Method ANOVA
Comments Nonparametric ANOVA Model: Rank of Variable=Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group. Hypoglycemic Rate (1 year) was used.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.102
Comments P-value for Severe Hypoglycemic Rate.
Method ANOVA
Comments Nonparametric ANOVA Model: Rank of Variable=Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group. Hypoglycemic Rate (1 year) was used.
8.Secondary Outcome
Title 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall
Hide Description Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 30-day adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 30 days.
Time Frame Baseline to 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 229 229
Mean (Standard Deviation)
Unit of Measure: hypoglycemic events per 30 days
Hypoglycemic Rate 1.98  (2.36) 1.88  (2.54)
Nocturnal Hypoglycemic Rate 0.50  (0.87) 0.34  (0.77)
Severe Hypoglycemic Rate 0.01  (0.05) 0.00  (0.02)
9.Secondary Outcome
Title Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint
Hide Description [Not Specified]
Time Frame Baseline, 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 229 229
Mean (Standard Deviation)
Unit of Measure: kilograms (kg)
Baseline 84.23  (16.83) 86.05  (18.62)
Change from Baseline 1.04  (3.45) 1.07  (3.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments Hypothesis: insulin lispro protamine suspension is noninferior to glargine with regard to change in absolute body weight from baseline to endpoint.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Noninferiority margin of 1.5 kilograms (kg).
Statistical Test of Hypothesis P-Value 0.975
Comments P-value for Change from Baseline.
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Baseline + Country + Baseline HbA1c + Baseline Sulfonylurea Group.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.01
Confidence Interval 95%
-0.61 to 0.59
Estimation Comments The two-sided 95% confidence interval is for the Least Squares Mean difference between the two treatments (Insulin Lispro Protamine Suspension minus Glargine).
10.Secondary Outcome
Title Total Daily Insulin Dose (Units) at Endpoint
Hide Description Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units).
Time Frame 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement. Last observation carried forward.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 229 228
Mean (Standard Deviation)
Unit of Measure: Units of insulin
33.28  (21.84) 30.85  (20.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.031
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group + Change in HbA1c from Baseline.
11.Secondary Outcome
Title Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint
Hide Description Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (units/kilograms).
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement. Last observation carried forward.
Arm/Group Title Lispro Glargine
Hide Arm/Group Description:
Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Overall Number of Participants Analyzed 229 228
Mean (Standard Deviation)
Unit of Measure: Units of insulin/kilograms (U/kg)
0.39  (0.24) 0.35  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lispro, Glargine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA Model: Variable = Treatment + Country + Baseline HbA1c + Baseline Sulfonylurea Group + Change in HbA1c from Baseline.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lispro Glargine
Hide Arm/Group Description Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
All-Cause Mortality
Lispro Glargine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lispro Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/229 (1.75%)      10/229 (4.37%)    
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Cardiac disorders     
Acute myocardial infarction  1  1/229 (0.44%)  1 0/229 (0.00%)  0
Angina unstable  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Cardiac failure  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Ear and labyrinth disorders     
Vertigo positional  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Eye disorders     
Retinal ischaemia  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Hepatobiliary disorders     
Cholelithiasis  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Infections and infestations     
Gastroenteritis  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Urinary tract infection  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Injury, poisoning and procedural complications     
Fall  1  1/229 (0.44%)  1 0/229 (0.00%)  0
Tibia fracture  1  1/229 (0.44%)  1 0/229 (0.00%)  0
Metabolism and nutrition disorders     
Diabetic foot  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Diabetic ketoacidosis  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Hypoglycaemia  1  1/229 (0.44%)  1 0/229 (0.00%)  0
Nervous system disorders     
Lacunar infarction  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Reproductive system and breast disorders     
Postmenopausal haemorrhage  1  1/229 (0.44%)  1 0/229 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/229 (0.00%)  0 1/229 (0.44%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Lispro Glargine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   100/229 (43.67%)      109/229 (47.60%)    
Gastrointestinal disorders     
Abdominal pain  1  3/229 (1.31%)  3 3/229 (1.31%)  4
Diarrhoea  1  9/229 (3.93%)  9 7/229 (3.06%)  7
Dyspepsia  1  2/229 (0.87%)  2 3/229 (1.31%)  3
Gastritis  1  3/229 (1.31%)  3 1/229 (0.44%)  1
Nausea  1  1/229 (0.44%)  1 8/229 (3.49%)  8
Vomiting  1  4/229 (1.75%)  4 2/229 (0.87%)  2
General disorders     
Chest pain  1  3/229 (1.31%)  3 4/229 (1.75%)  6
Fatigue  1  3/229 (1.31%)  3 1/229 (0.44%)  1
Oedema peripheral  1  3/229 (1.31%)  3 2/229 (0.87%)  2
Pyrexia  1  4/229 (1.75%)  5 1/229 (0.44%)  1
Infections and infestations     
Bronchitis  1  4/229 (1.75%)  4 2/229 (0.87%)  2
Gastroenteritis  1  1/229 (0.44%)  1 4/229 (1.75%)  4
Influenza  1  8/229 (3.49%)  10 11/229 (4.80%)  12
Nasopharyngitis  1  10/229 (4.37%)  10 17/229 (7.42%)  17
Respiratory tract infection  1  3/229 (1.31%)  3 0/229 (0.00%)  0
Tooth infection  1  0/229 (0.00%)  0 3/229 (1.31%)  3
Upper respiratory tract infection  1  8/229 (3.49%)  10 5/229 (2.18%)  5
Urinary tract infection  1  2/229 (0.87%)  2 3/229 (1.31%)  4
Musculoskeletal and connective tissue disorders     
Arthralgia  1  4/229 (1.75%)  6 6/229 (2.62%)  6
Back pain  1  6/229 (2.62%)  6 8/229 (3.49%)  9
Neck pain  1  3/229 (1.31%)  5 1/229 (0.44%)  1
Pain in extremity  1  6/229 (2.62%)  7 7/229 (3.06%)  7
Nervous system disorders     
Diabetic neuropathy  1  0/229 (0.00%)  0 3/229 (1.31%)  3
Dizziness  1  1/229 (0.44%)  1 6/229 (2.62%)  6
Headache  1  15/229 (6.55%)  25 12/229 (5.24%)  22
Paraesthesia  1  4/229 (1.75%)  5 2/229 (0.87%)  2
Psychiatric disorders     
Anxiety  1  4/229 (1.75%)  5 5/229 (2.18%)  5
Insomnia  1  4/229 (1.75%)  4 1/229 (0.44%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/229 (1.75%)  7 6/229 (2.62%)  6
Pharyngolaryngeal pain  1  2/229 (0.87%)  3 3/229 (1.31%)  4
Sinus congestion  1  3/229 (1.31%)  3 0/229 (0.00%)  0
Skin and subcutaneous tissue disorders     
Dermatitis allergic  1  1/229 (0.44%)  1 3/229 (1.31%)  3
Vascular disorders     
Hypertension  1  6/229 (2.62%)  8 2/229 (0.87%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT00510952     History of Changes
Other Study ID Numbers: 11813
F3Z-MC-IOPE ( Other Identifier: Eli Lilly and Company )
First Submitted: August 1, 2007
First Posted: August 3, 2007
Results First Submitted: September 25, 2009
Results First Posted: November 3, 2009
Last Update Posted: October 21, 2010