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 detemir as basal insulin therapy in adults with type 2 diabetes. A gatekeeper strategy will be employed for sequentially testing the secondary objectives.
Interventions
Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks.
DRUGDetemir
Patient specific dose administered subcutaneously once or twice daily 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
1. Have type 2 diabetes mellitus for at least 1 year. 2. Are at least 18 years old. 3. 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, at or above the doses defined in the following: Metformin--1500 milligrams per day (mg/day); Sulfonylureas--1/2 the maximum daily dose, according to the local package insert; Dipeptidyl peptidase-intravenous (DPP-IV) inhibitors-- 1/2 the maximum daily dose, according to the local package insert; Thiazolidinediones (TZDs)--30 mg/day pioglitazone or 4 mg/day rosiglitazone. 4. 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. 5. Body mass index (BMI) greater than or equal to 25 and less than or equal to 45 kilograms per square meter (kg/m2).
Exclusion criteria
1. 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. 2. 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. 3. 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. 4. Have a history of renal transplantation or are currently receiving renal dialysis or creatinine greater than or equal to 2.0 milligrams per deciliter (mg/dL) (177 micromoles per liter \[micromol/L\]). 5. Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease (alanine transaminase \[ALT\], or aspartate transaminase \[AST\] greater than 2 times the upper limit of the reference range, as defined by the local laboratory) or have albumin value above or below the normal reference range, as defined by the local laboratory.
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 |
|---|---|---|
| Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Baseline, 12 Weeks, 24 Weeks | — |
| Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint | 24 Weeks | Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7.0% and less than or equal to 6.5% at endpoint. |
| Glycemic Variability | 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) for the actual morning pre-meal blood glucose value. |
| 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | 24 Weeks | Actual daily mean blood glucose levels at endpoint. |
| Total Daily Insulin Dose (Units) at Endpoint | 24 Weeks | Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units). |
| Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | 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. Results are for the combined titration and maintenance periods. |
| 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. |
| 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 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). |
| Number of Injections of Basal Insulin Analog at Endpoint | 24 Weeks | — |
Countries
Argentina, Hungary, India, Mexico, Poland, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
789 patients were screened; 347 patients failed screening or discontinued before randomization. Demographics and outcomes are reported on the Full Analysis Set: all randomized patients who received at least one dose of study drug and had at least one post-baseline measurement for the dependent variable, according to Intent to Treat principles.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro Protamine Suspension Insulin Lispro Protamine Suspension: Patient specific dose administered subcutaneously once daily or twice daily x 24 weeks. | 219 |
| Detemir Detemir: Patient specific dose administered subcutaneously once daily x 24 weeks. | 210 |
| Total | 429 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Entry Criteria Not Met | 1 | 4 |
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Physician Decision | 3 | 5 |
| Overall Study | Protocol Violation | 8 | 5 |
| Overall Study | Sponsor Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 13 | 14 |
Baseline characteristics
| Characteristic | Insulin Lispro Protamine Suspension | Detemir | Total |
|---|---|---|---|
| Age Continuous | 56.32 years STANDARD_DEVIATION 9.91 | 55.73 years STANDARD_DEVIATION 10.2 | 56.03 years STANDARD_DEVIATION 10.04 |
| Body Mass Index (BMI) | 30.03 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.01 | 30.10 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.12 | 30.06 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 5.06 |
| Body Weight | 81.10 kilograms (kg) STANDARD_DEVIATION 17.46 | 82.72 kilograms (kg) STANDARD_DEVIATION 19.32 | 81.89 kilograms (kg) STANDARD_DEVIATION 18.39 |
| Duration of Diabetes | 9.48 years STANDARD_DEVIATION 6.09 | 8.94 years STANDARD_DEVIATION 5.59 | 9.22 years STANDARD_DEVIATION 5.85 |
| Height | 163.94 centimeters (cm) STANDARD_DEVIATION 10.19 | 165.14 centimeters (cm) STANDARD_DEVIATION 10.94 | 164.53 centimeters (cm) STANDARD_DEVIATION 10.57 |
| Race/Ethnicity African | 8 participants | 8 participants | 16 participants |
| Race/Ethnicity Caucasian | 88 participants | 82 participants | 170 participants |
| Race/Ethnicity East Asian | 35 participants | 33 participants | 68 participants |
| Race/Ethnicity Hispanic | 45 participants | 47 participants | 92 participants |
| Race/Ethnicity West Asian | 43 participants | 40 participants | 83 participants |
| Region of Enrollment Argentina | 10 participants | 11 participants | 21 participants |
| Region of Enrollment Hungary | 36 participants | 34 participants | 70 participants |
| Region of Enrollment India | 42 participants | 39 participants | 81 participants |
| Region of Enrollment Korea, Republic of | 10 participants | 11 participants | 21 participants |
| Region of Enrollment Mexico | 28 participants | 27 participants | 55 participants |
| Region of Enrollment Spain | 13 participants | 13 participants | 26 participants |
| Region of Enrollment Taiwan | 20 participants | 19 participants | 39 participants |
| Region of Enrollment United States | 60 participants | 56 participants | 116 participants |
| Sex: Female, Male Female | 108 Participants | 97 Participants | 205 Participants |
| Sex: Female, Male Male | 111 Participants | 113 Participants | 224 Participants |
| Sulfonylurea Group No | 49 participants | 51 participants | 100 participants |
| Sulfonylurea Group Unavailable | 0 participants | 1 participants | 1 participants |
| Sulfonylurea Group Yes | 170 participants | 158 participants | 328 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 78 / 219 | 70 / 210 |
| serious Total, serious adverse events | 7 / 219 | 1 / 210 |
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 at least one post-baseline measurement. Last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro Protamine Suspension | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Baseline (n=209, n=202) | 8.79 percent of HbA1c | Standard Error 0.06 |
| Insulin Lispro Protamine Suspension | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Change from Baseline (n=209, n=202) | -1.52 percent of HbA1c | Standard Error 0.08 |
| Detemir | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Baseline (n=209, n=202) | 8.77 percent of HbA1c | Standard Error 0.06 |
| Detemir | Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) | Change from Baseline (n=209, n=202) | -1.31 percent of HbA1c | Standard Error 0.08 |
Comparison: Hypothesis: Basal analog insulin lispro protamine suspension, injected once or twice daily is noninferior to basal analog insulin determir, injected once or twice daily, with regard to glycemic control as measured by change in HbA1c from baseline to endpoint (last observation carried forward).p-value: 0.02695% CI: [-0.39, -0.03]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 at least one post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro Protamine Suspension | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 24.23 hypoglycemic events per 1 year | Standard Deviation 32.99 |
| Insulin Lispro Protamine Suspension | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 6.32 hypoglycemic events per 1 year | Standard Deviation 12.11 |
| Insulin Lispro Protamine Suspension | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Severe Hypoglycemic Rate | 0.05 hypoglycemic events per 1 year | Standard Deviation 0.45 |
| Detemir | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 16.23 hypoglycemic events per 1 year | Standard Deviation 26.05 |
| Detemir | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 3.75 hypoglycemic events per 1 year | Standard Deviation 13.18 |
| Detemir | 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Severe Hypoglycemic Rate | 0.01 hypoglycemic events per 1 year | Standard Deviation 0.15 |
p-value: 0.001ANOVA
p-value: 0.001ANOVA
p-value: 0.226ANOVA
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 at least one post-baseline measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro Protamine Suspension | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 1.99 hypoglycemic events per 30 days | Standard Deviation 2.71 |
| Insulin Lispro Protamine Suspension | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 0.52 hypoglycemic events per 30 days | Standard Deviation 0.99 |
| Insulin Lispro Protamine Suspension | 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 0.04 |
| Detemir | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Hypoglycemic Rate | 1.33 hypoglycemic events per 30 days | Standard Deviation 2.14 |
| Detemir | 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Nocturnal Hypoglycemic Rate | 0.31 hypoglycemic events per 30 days | Standard Deviation 1.08 |
| Detemir | 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 0.01 |
Secondary
7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint
Actual 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 |
|---|---|---|---|---|
| Insulin Lispro Protamine Suspension | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average Pre-Meal | 7.48 millimoles per liter (mmol/L) | Standard Deviation 1.69 |
| Insulin Lispro Protamine Suspension | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average Post-Meal | 9.37 millimoles per liter (mmol/L) | Standard Deviation 1.91 |
| Insulin Lispro Protamine Suspension | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average Morning+Evening Pre-Meal | 7.49 millimoles per liter (mmol/L) | Standard Deviation 1.68 |
| Insulin Lispro Protamine Suspension | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average 7-Point SMBG | 8.25 millimoles per liter (mmol/L) | Standard Deviation 1.58 |
| Detemir | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average 7-Point SMBG | 8.26 millimoles per liter (mmol/L) | Standard Deviation 1.73 |
| Detemir | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average Pre-Meal | 7.43 millimoles per liter (mmol/L) | Standard Deviation 1.69 |
| Detemir | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average Morning+Evening Pre-Meal | 7.40 millimoles per liter (mmol/L) | Standard Deviation 1.86 |
| Detemir | 7-point Self-monitored Blood Glucose (SMBG) Profile at Endpoint | Average Post-Meal | 9.42 millimoles per liter (mmol/L) | Standard Deviation 2.21 |
p-value: 0.952ANOVA
p-value: 0.856ANOVA
p-value: 0.79ANOVA
p-value: 0.632ANOVA
Secondary
Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks
Time frame: Baseline, 12 Weeks, 24 Weeks
Population: Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro Protamine Suspension | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 12 HbA1c | 7.44 percent hemoglobin | Standard Error 0.08 |
| Insulin Lispro Protamine Suspension | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 24 HbA1c | 7.14 percent hemoglobin | Standard Error 0.09 |
| Insulin Lispro Protamine Suspension | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 12 Change from Baseline | -1.33 percent hemoglobin | Standard Error 0.08 |
| Insulin Lispro Protamine Suspension | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 24 Change from Baseline | -1.63 percent hemoglobin | Standard Error 0.09 |
| Insulin Lispro Protamine Suspension | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Baseline | 8.79 percent hemoglobin | Standard Error 0.06 |
| Detemir | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 24 Change from Baseline | -1.43 percent hemoglobin | Standard Error 0.08 |
| Detemir | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Baseline | 8.77 percent hemoglobin | Standard Error 0.06 |
| Detemir | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 12 HbA1c | 7.55 percent hemoglobin | Standard Error 0.07 |
| Detemir | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 12 Change from Baseline | -1.22 percent hemoglobin | Standard Error 0.07 |
| Detemir | Actual and Change From Baseline Hemoglobin A1c (HbA1c) Value at 12 Weeks and at 24 Weeks | Week 24 HbA1c | 7.34 percent hemoglobin | Standard Error 0.08 |
p-value: 0.21395% CI: [-0.28, 0.06]ANCOVA
p-value: 0.21395% CI: [-0.28, 0.06]ANCOVA
p-value: 0.03895% CI: [-0.38, -0.01]ANCOVA
p-value: 0.03895% CI: [-0.38, -0.01]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 at least one post-baseline measurement. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro Protamine Suspension | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Baseline | 81.10 kilograms (kg) | Standard Deviation 17.46 |
| Insulin Lispro Protamine Suspension | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Change from Baseline | 1.88 kilograms (kg) | Standard Deviation 3.16 |
| Detemir | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Baseline | 82.56 kilograms (kg) | Standard Deviation 19.22 |
| Detemir | Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint | Change from Baseline | 0.36 kilograms (kg) | Standard Deviation 2.85 |
Comparison: The second gatekeeping hypothesis was that Insulin Lispro Protamine Suspension was noninferior to detemir with regard to change in absolute body weight from baseline to endpoint (last observation carried forward).p-value: <0.00195% CI: [0.93, 2.06]ANCOVA
Secondary
Glycemic Variability
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) for the actual morning pre-meal blood glucose value.
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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro Protamine Suspension | Glycemic Variability | 1.14 millimoles per Liter (mmol/L) | Standard Deviation 0.64 |
| Detemir | Glycemic Variability | 1.04 millimoles per Liter (mmol/L) | Standard Deviation 0.69 |
Comparison: The first gatekeeping hypothesis was that Insulin Lispro Protamine Suspension was noninferior to determir.p-value: 0.10795% CI: [-0.02, 0.23]ANOVA
Secondary
Number of Injections of Basal Insulin Analog 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 (NUMBER) |
|---|---|---|---|
| Insulin Lispro Protamine Suspension | Number of Injections of Basal Insulin Analog at Endpoint | Patients with 1 Injection | 89 participants |
| Insulin Lispro Protamine Suspension | Number of Injections of Basal Insulin Analog at Endpoint | Patients with 2 Injections | 130 participants |
| Detemir | Number of Injections of Basal Insulin Analog at Endpoint | Patients with 1 Injection | 108 participants |
| Detemir | Number of Injections of Basal Insulin Analog at Endpoint | Patients with 2 Injections | 102 participants |
p-value: 0.026Fisher Exact
Secondary
Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods
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. Results are for the combined titration and maintenance periods.
Time frame: Baseline to 24 Weeks
Population: Number of randomized patients who received at least one dose of study drug and at least one post-baseline measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro Protamine Suspension | Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | All Hypoglycemic Episodes | 151 participants |
| Insulin Lispro Protamine Suspension | Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | Nocturnal Hypoglycemic Episodes | 99 participants |
| Insulin Lispro Protamine Suspension | Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | Severe Hypoglycemic Episodes (N=214, N=207) | 5 participants |
| Detemir | Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | All Hypoglycemic Episodes | 137 participants |
| Detemir | Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | Nocturnal Hypoglycemic Episodes | 68 participants |
| Detemir | Number of Participants With Self-reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall for All Study Periods | Severe Hypoglycemic Episodes (N=214, N=207) | 2 participants |
p-value: 0.45Fisher Exact
p-value: 0.472Fisher Exact
p-value: 0.005Fisher Exact
Secondary
Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint
Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7.0% 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 at least one post-baseline measurement. Last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro Protamine Suspension | Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint | HbA1c <7.0% | 34.9 percentage of participants |
| Insulin Lispro Protamine Suspension | Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint | HbA1c ≤6.5% | 22.5 percentage of participants |
| Detemir | Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint | HbA1c <7.0% | 31.2 percentage of participants |
| Detemir | Percentage of Patients With HbA1c <7.0% and HbA1c < or = 6.5% at Endpoint | HbA1c ≤6.5% | 16.3 percentage of participants |
p-value: 0.463Fisher Exact
p-value: 0.135Fisher 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 at least one post-baseline measurement. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro Protamine Suspension | Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint | 0.39 Units of Insulin/kilograms (U/kg) | Standard Deviation 0.23 |
| Detemir | Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint | 0.46 Units of Insulin/kilograms (U/kg) | Standard Deviation 0.36 |
p-value: 0.039ANCOVA
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 at least one post-baseline measurement. Last observation carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro Protamine Suspension | Total Daily Insulin Dose (Units) at Endpoint | 31.78 Units of insulin | Standard Deviation 19.14 |
| Detemir | Total Daily Insulin Dose (Units) at Endpoint | 37.30 Units of insulin | Standard Deviation 29.45 |
p-value: 0.074ANCOVA