Diabetes Mellitus, Type 2
Conditions
Keywords
diabetes, type 2
Brief summary
The purpose of this study is to examine the effectiveness and safety of insulin lispro protamine suspension (ILPS) as compared to insulin glargine as basal insulin therapy in adults with type 2 diabetes.
Interventions
Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
DRUGInsulin Glargine
Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes mellitus for at least 1 year. * Are greater than or equal to 18 years old. * Have been receiving oral antihyperglycemic medications (OAMs), without insulin, for at least 3 months immediately prior to the study and have been on stable doses of at least 2 of the following OAMs for the 6 weeks prior to Visit 1: Metformin- Sulfonylureas-Dipeptidyl peptidase-IV (DPP-IV) inhibitors-Thiazolidinediones (TZDs) * Have a hemoglobin A1c (HbA1c) greater than or equal to 7.5% and less than or equal to 10.0%, as measured by a central laboratory before Visit 2. * Body mass index (BMI) greater than or equal to 25 and less than or equal to 45 kg/meter squared.
Exclusion criteria
* Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks. * Have taken any glucose-lowering medications not included in Inclusion Criterion #3; (for example, acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide) in the past 3 months before Visit 1. * Have had more than 1 episode of severe hypoglycemia, within 6 months prior to entry into the study, or is currently diagnosed as having hypoglycemia unawareness. * Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months. * Are pregnant or intend to become pregnant during the course of the study or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Baseline, 24 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint | 24 weeks | Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7% and less than or equal to 6.5% at endpoint. |
| Glycemic Variability at Endpoint | 24 weeks | 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. |
| 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | 24 weeks | Actual measurements and daily mean blood glucose levels at endpoint. |
| Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | Baseline to 24 weeks | 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. |
| Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Baseline, 12 Weeks, 24 Weeks | — |
| 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Baseline to 24 Weeks | 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. |
| Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Baseline, 24 weeks | — |
| Total Daily Insulin Dose (Units) at Endpoint | 24 weeks | Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units). |
| Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint | 24 Weeks | Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (units/kilograms). |
| 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Baseline to 24 weeks | 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. |
Countries
Brazil, Canada, Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lispro Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks | 229 |
| Glargine Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks | 229 |
| Total | 458 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Did Not Receive Study Drug | 2 | 0 |
| Overall Study | Entry Criteria Not Met | 3 | 1 |
| Overall Study | Lost to Follow-up | 5 | 3 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 7 | 4 |
| Overall Study | Sponsor Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 7 |
Baseline characteristics
| Characteristic | Lispro | Total | Glargine |
|---|---|---|---|
| Age Continuous | 58.05 years STANDARD_DEVIATION 9.35 | 57.67 years STANDARD_DEVIATION 9.17 | 57.29 years STANDARD_DEVIATION 8.99 |
| Body Mass Index (BMI) | 30.69 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.01 | 31.16 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.27 | 31.62 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.48 |
| Body Weight | 84.23 kilograms (kg) STANDARD_DEVIATION 16.83 | 85.14 kilograms (kg) STANDARD_DEVIATION 17.75 | 86.05 kilograms (kg) STANDARD_DEVIATION 18.62 |
| Duration of Diabetes | 9.80 years STANDARD_DEVIATION 6.45 | 9.85 years STANDARD_DEVIATION 6.47 | 9.90 years STANDARD_DEVIATION 6.51 |
| Height | 165.45 centimeters (cm) STANDARD_DEVIATION 10.04 | 165.03 centimeters (cm) STANDARD_DEVIATION 10.07 | 164.62 centimeters (cm) STANDARD_DEVIATION 10.11 |
| Race/Ethnicity African | 11 participants | 25 participants | 14 participants |
| Race/Ethnicity Caucasian | 147 participants | 289 participants | 142 participants |
| Race/Ethnicity East Asian | 10 participants | 25 participants | 15 participants |
| Race/Ethnicity Hispanic | 33 participants | 59 participants | 26 participants |
| Race/Ethnicity Native American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity West Asian (Indian sub-continent) | 28 participants | 59 participants | 31 participants |
| Region of Enrollment Argentina | 13 participants | 25 participants | 12 participants |
| Region of Enrollment Brazil | 18 participants | 37 participants | 19 participants |
| Region of Enrollment Canada | 20 participants | 40 participants | 20 participants |
| Region of Enrollment India | 27 participants | 58 participants | 31 participants |
| Region of Enrollment Korea, Republic of | 9 participants | 22 participants | 13 participants |
| Region of Enrollment Mexico | 18 participants | 34 participants | 16 participants |
| Region of Enrollment Poland | 52 participants | 102 participants | 50 participants |
| Region of Enrollment Russian Federation | 30 participants | 59 participants | 29 participants |
| Region of Enrollment Spain | 9 participants | 19 participants | 10 participants |
| Region of Enrollment United States | 33 participants | 62 participants | 29 participants |
| Sex: Female, Male Female | 107 Participants | 223 Participants | 116 Participants |
| Sex: Female, Male Male | 122 Participants | 235 Participants | 113 Participants |
| Sulfonylurea Group No | 38 participants | 77 participants | 39 participants |
| Sulfonylurea Group Yes | 191 participants | 381 participants | 190 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 100 / 229 | 109 / 229 |
| serious Total, serious adverse events | 4 / 229 | 10 / 229 |
Outcome results
Primary
Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c)
Time frame: Baseline, 24 Weeks
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Baseline | 8.70 percent of HbA1c | Standard Error 0.06 |
| Lispro | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Change from Baseline | -1.46 percent of HbA1c | Standard Error 0.07 |
| Glargine | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Baseline | 8.69 percent of HbA1c | Standard Error 0.06 |
| Glargine | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Change from Baseline | -1.41 percent of HbA1c | Standard Error 0.07 |
Comparison: 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).p-value: 0.55195% CI: [-0.21, 0.11]ANCOVA
Secondary
1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall
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
Population: Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 24.16 hypoglycemic event per 1 year | Standard Deviation 28.78 |
| Lispro | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 6.08 hypoglycemic event per 1 year | Standard Deviation 10.62 |
| Lispro | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Severe Hypoglycemic Rate | 0.11 hypoglycemic event per 1 year | Standard Deviation 0.58 |
| Glargine | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 22.95 hypoglycemic event per 1 year | Standard Deviation 30.87 |
| Glargine | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 4.08 hypoglycemic event per 1 year | Standard Deviation 9.4 |
| Glargine | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Severe Hypoglycemic Rate | 0.02 hypoglycemic event per 1 year | Standard Deviation 0.21 |
p-value: 0.316ANOVA
p-value: <0.001ANOVA
p-value: 0.102ANOVA
Secondary
30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall
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
Population: Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 1.98 hypoglycemic events per 30 days | Standard Deviation 2.36 |
| Lispro | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 0.50 hypoglycemic events per 30 days | Standard Deviation 0.87 |
| Lispro | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Severe Hypoglycemic Rate | 0.01 hypoglycemic events per 30 days | Standard Deviation 0.05 |
| Glargine | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 1.88 hypoglycemic events per 30 days | Standard Deviation 2.54 |
| Glargine | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 0.34 hypoglycemic events per 30 days | Standard Deviation 0.77 |
| Glargine | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Severe Hypoglycemic Rate | 0.00 hypoglycemic events per 30 days | Standard Deviation 0.02 |
Secondary
7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint
Actual measurements and daily mean blood glucose levels at endpoint.
Time frame: 24 weeks
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Midday Postprandial Meal | 9.09 millimoles per liter (mmol/L) | Standard Deviation 2.52 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual 0300 Hours | 6.79 millimoles per liter (mmol/L) | Standard Deviation 2.05 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Midday Pre-Meal | 6.93 millimoles per liter (mmol/L) | Standard Deviation 2.11 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean 7-Point SMBG | 7.79 millimoles per liter (mmol/L) | Standard Deviation 1.82 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Evening Pre-Meal | 7.50 millimoles per liter (mmol/L) | Standard Deviation 2.06 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean Pre-Meal | 6.99 millimoles per liter (mmol/L) | Standard Deviation 1.77 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Morning Postprandial Meal | 8.64 millimoles per liter (mmol/L) | Standard Deviation 2.48 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean Postprandial Meal | 8.96 millimoles per liter (mmol/L) | Standard Deviation 2.25 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Evening Postprandial Meal | 9.19 millimoles per liter (mmol/L) | Standard Deviation 2.84 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean Morning+Evening Pre-Meal | 6.99 millimoles per liter (mmol/L) | Standard Deviation 1.51 |
| Lispro | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Morning Pre-Meal | 6.47 millimoles per liter (mmol/L) | Standard Deviation 1.4 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean Morning+Evening Pre-Meal | 6.93 millimoles per liter (mmol/L) | Standard Deviation 1.41 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Morning Pre-Meal | 6.33 millimoles per liter (mmol/L) | Standard Deviation 1.36 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Morning Postprandial Meal | 9.00 millimoles per liter (mmol/L) | Standard Deviation 2.55 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Midday Pre-Meal | 7.16 millimoles per liter (mmol/L) | Standard Deviation 2.07 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Midday Postprandial Meal | 9.17 millimoles per liter (mmol/L) | Standard Deviation 2.5 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Evening Pre-Meal | 7.54 millimoles per liter (mmol/L) | Standard Deviation 2.02 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual Evening Postprandial Meal | 9.29 millimoles per liter (mmol/L) | Standard Deviation 2.54 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual 0300 Hours | 7.00 millimoles per liter (mmol/L) | Standard Deviation 2.21 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean 7-Point SMBG | 7.96 millimoles per liter (mmol/L) | Standard Deviation 1.74 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean Pre-Meal | 7.04 millimoles per liter (mmol/L) | Standard Deviation 1.55 |
| Glargine | 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Daily Mean Postprandial Meal | 9.18 millimoles per liter (mmol/L) | Standard Deviation 2.2 |
p-value: 0.302ANOVA
p-value: 0.144ANOVA
p-value: 0.279ANOVA
p-value: 0.928ANOVA
p-value: 0.918ANOVA
p-value: 0.875ANOVA
p-value: 0.316ANOVA
p-value: 0.389ANOVA
p-value: 0.836ANOVA
p-value: 0.394ANOVA
p-value: 0.609ANOVA
Secondary
Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value
Time frame: Baseline, 12 Weeks, 24 Weeks
Population: Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 12 HbA1c (n=213, n=220) | 7.30 percent hemoglobin | Standard Error 0.07 |
| Lispro | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 24 HbA1c (n=206, n=218) | 7.15 percent hemoglobin | Standard Error 0.07 |
| Lispro | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 12 Change from Baseline (n=213, n=220) | -1.36 percent hemoglobin | Standard Error 0.07 |
| Lispro | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 24 Change from Baseline (n=206, n=218) | -1.52 percent hemoglobin | Standard Error 0.07 |
| Lispro | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Baseline (n= 225, n= 226) | 8.70 percent hemoglobin | Standard Error 0.06 |
| Glargine | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 24 Change from Baseline (n=206, n=218) | -1.43 percent hemoglobin | Standard Error 0.07 |
| Glargine | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Baseline (n= 225, n= 226) | 8.69 percent hemoglobin | Standard Error 0.06 |
| Glargine | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 12 HbA1c (n=213, n=220) | 7.36 percent hemoglobin | Standard Error 0.07 |
| Glargine | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 12 Change from Baseline (n=213, n=220) | -1.30 percent hemoglobin | Standard Error 0.07 |
| Glargine | Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value | Week 24 HbA1c (n=206, n=218) | 7.24 percent hemoglobin | Standard Error 0.07 |
p-value: 0.42795% CI: [-0.21, 0.09]ANCOVA
p-value: 0.42795% CI: [-0.21, 0.09]ANCOVA
p-value: 0.25495% CI: [-0.25, 0.07]ANCOVA
p-value: 0.25495% CI: [-0.25, 0.07]ANCOVA
Secondary
Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint
Time frame: Baseline, 24 weeks
Population: Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lispro | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Baseline | 84.23 kilograms (kg) | Standard Deviation 16.83 |
| Lispro | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Change from Baseline | 1.04 kilograms (kg) | Standard Deviation 3.45 |
| Glargine | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Baseline | 86.05 kilograms (kg) | Standard Deviation 18.62 |
| Glargine | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Change from Baseline | 1.07 kilograms (kg) | Standard Deviation 3.25 |
Comparison: Hypothesis: insulin lispro protamine suspension is noninferior to glargine with regard to change in absolute body weight from baseline to endpoint.p-value: 0.97595% CI: [-0.61, 0.59]ANCOVA
Secondary
Glycemic Variability at Endpoint
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lispro | Glycemic Variability at Endpoint | 1.01 millimoles per liter (mmol/L) | Standard Deviation 0.72 |
| Glargine | Glycemic Variability at Endpoint | 0.94 millimoles per liter (mmol/L) | Standard Deviation 0.71 |
Comparison: Hypothesis: Insulin lispro protamine suspension is noninferior to glargine at actual morning pre-meal at endpoint.p-value: 0.32395% CI: [-0.06, 0.19]ANOVA
Secondary
Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall
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
Population: Number of randomized patients who received at least one dose of study drug and had at least one post-baseline measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lispro | Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | All Hypoglycemic Episodes | 168 participants |
| Lispro | Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | Nocturnal Hypoglycemic Episodes | 114 participants |
| Lispro | Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | Severe Hypoglycemic Episodes | 9 participants |
| Glargine | Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | All Hypoglycemic Episodes | 160 participants |
| Glargine | Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | Nocturnal Hypoglycemic Episodes | 87 participants |
| Glargine | Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | Severe Hypoglycemic Episodes | 2 participants |
p-value: 0.468Fisher Exact
p-value: 0.011Fisher Exact
p-value: 0.036Fisher Exact
Secondary
Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lispro | Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint | HbA1c <7.0% | 43.8 percentage of participants |
| Lispro | Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint | HbA1c ≤6.5% | 24.8 percentage of participants |
| Glargine | Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint | HbA1c <7.0% | 41.2 percentage of participants |
| Glargine | Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint | HbA1c ≤6.5% | 21.7 percentage of participants |
p-value: 0.634Fisher Exact
p-value: 0.504Fisher Exact
Secondary
Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint
Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (units/kilograms).
Time frame: 24 Weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lispro | Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint | 0.39 Units of insulin/kilograms (U/kg) | Standard Deviation 0.24 |
| Glargine | Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint | 0.35 Units of insulin/kilograms (U/kg) | Standard Deviation 0.2 |
p-value: 0.015ANCOVA
Secondary
Total Daily Insulin Dose (Units) at Endpoint
Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units).
Time frame: 24 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lispro | Total Daily Insulin Dose (Units) at Endpoint | 33.28 Units of insulin | Standard Deviation 21.84 |
| Glargine | Total Daily Insulin Dose (Units) at Endpoint | 30.85 Units of insulin | Standard Deviation 20.46 |
p-value: 0.031ANCOVA