Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of the study is to compare the insulin lispro low mixture (1, 2 or 3 daily injections) with insulin glargine (alone or with 1, 2 or 3 insulin lispro daily injections) on lowering the blood sugar level
Interventions
Dose depending on patient's need; subcutaneous injection before meal; start with once-daily injection before evening meal for 48 weeks, may add second injection before breakfast at any time during the treatment period if required, and may further add third injection before lunch at any time in the remainder of the treatment period if required.
DRUGInsulin glargine
Dose depending on patient's need; one daily subcutaneous injection before bedtime for 48 weeks
DRUGInsulin lispro
Dose depending on patient's need; subcutaneous injection before meal; may start once-daily injection before meal (e.g. lunch if the highest blood glucose value is measured before dinner) on top of insulin glargine at any time of the treatment period if required, and may further add second or even third injection in the remainder of the treatment period if required.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus * Receiving oral antihyperglycemic medications (including metformin) without insulin injection in the last 90 days * Hemoglobin A1c (HbA1c) equal to or greater than 7.0% but less than 11.0% * Willing to receive insulin injection while continuing to take the prestudy oral antihyperglycemic medications * Able to perform self monitoring of blood glucose
Exclusion criteria
* Are taking any other glucose-lowering agents other than metformin, sulfonylurea or Thiazolidinedione (Pioglitazone) * Have taken acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide in the past 6 weeks, or for a total of 30 days or more, in the last 24 weeks * Have a body mass index greater than 35 kg/m2 * History or presence of kidney disease * Have cardiac disease (Class III or IV)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline to 48 Week Endpoint in Hemoglobin A1c (HbA1c) | Baseline, 48 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1c (HbA1c) Over Time | Baseline, 16 Weeks, 32 Weeks, 48 Weeks | — |
| Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | 16 weeks, 32 weeks, 48 weeks | — |
| 7-point Self-monitored Blood Glucose Profiles | Baseline, 16 weeks, 32 weeks, 48 weeks | — |
| Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | baseline, 48 weeks | — |
| Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks | 16 weeks, 32 weeks, 48 weeks | — |
| Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks | 16 weeks, 32 weeks, 48 weeks | — |
| Safety: Number of Participants With Serious and Non-Serious Adverse Events | baseline through 48 weeks | Safety was assessed via serious adverse events (SAEs) and AEs, the details of which are listed in the Reported Adverse Event section. |
| Change From Baseline in Postprandial Blood Glucose Over Time | Baseline, 16 weeks, 32 weeks, 48 weeks | The change in blood glucose was evaluated by the GlycoMark™ test. GlycoMark measures levels of 1,5 anhydroglucitol (1,5 AG) in serum or plasma, allowing for the short- to intermediate-term monitoring of glycemic control in patients with diabetes. When 1,5 AG values decrease, serum glucose levels increase. |
Countries
Australia, Brazil, Canada, China, India, Mexico, South Korea
Participant flow
Pre-assignment details
3 patients randomized but did not receive study drug: 1 withdrew, 1 did not want to use insulin, 1 lost to follow-up. Full Analysis Set: randomized, received at least 1 dose of study drug. Per-Protocol Set: randomized; no entry criteria violations; completed \>=32 weeks of study; no systemic glucocorticoid therapy \>14 cumulative days during study.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro LM Insulin lispro low mixture (1, 2 or 3 daily injections) | 211 |
| Insulin Glargine Insulin glargine (alone or with 1, 2 or 3 daily injections of insulin lispro) | 212 |
| Total | 423 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Entry Criteria Not Met | 2 | 2 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 9 | 3 |
| Overall Study | Physician Decision | 6 | 3 |
| Overall Study | Protocol Violation | 8 | 8 |
| Overall Study | Sponsor Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 4 |
Baseline characteristics
| Characteristic | Insulin Lispro LM | Insulin Glargine | Total |
|---|---|---|---|
| Age Continuous | 56.68 years STANDARD_DEVIATION 8.52 | 56.29 years STANDARD_DEVIATION 9.35 | 56.48 years STANDARD_DEVIATION 8.94 |
| Race/Ethnicity, Customized African | 8 participants | 16 participants | 24 participants |
| Race/Ethnicity, Customized Caucasian | 69 participants | 61 participants | 130 participants |
| Race/Ethnicity, Customized East Asian | 78 participants | 77 participants | 155 participants |
| Race/Ethnicity, Customized Hispanic | 35 participants | 36 participants | 71 participants |
| Race/Ethnicity, Customized Native American | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized West Asian | 20 participants | 22 participants | 42 participants |
| Race/Ethnicity, Customized West Asian (Indian sub-continent) | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Australia | 17 participants | 17 participants | 34 participants |
| Region of Enrollment Brazil | 33 participants | 34 participants | 67 participants |
| Region of Enrollment Canada | 28 participants | 28 participants | 56 participants |
| Region of Enrollment China | 29 participants | 30 participants | 59 participants |
| Region of Enrollment India | 53 participants | 53 participants | 106 participants |
| Region of Enrollment Korea, Republic of | 16 participants | 14 participants | 30 participants |
| Region of Enrollment Mexico | 35 participants | 36 participants | 71 participants |
| Sex: Female, Male Female | 118 Participants | 107 Participants | 225 Participants |
| Sex: Female, Male Male | 93 Participants | 105 Participants | 198 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 107 / 211 | 116 / 212 |
| serious Total, serious adverse events | 19 / 211 | 13 / 212 |
Outcome results
Primary
Change From Baseline to 48 Week Endpoint in Hemoglobin A1c (HbA1c)
Time frame: Baseline, 48 weeks
Population: Per-protocol set: randomized, no entry criteria violations, completed \>=32 weeks of study, and no systemic glucocorticoid therapy for \>14 cumulative days during study. Last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro LM | Change From Baseline to 48 Week Endpoint in Hemoglobin A1c (HbA1c) | -1.91 percent (%) glycated hemoglobin | Standard Error 0.23 |
| Insulin Glargine | Change From Baseline to 48 Week Endpoint in Hemoglobin A1c (HbA1c) | -1.87 percent (%) glycated hemoglobin | Standard Error 0.23 |
p-value: 0.71695% CI: [-0.25, 0.17]ANCOVA
Secondary
7-point Self-monitored Blood Glucose Profiles
Time frame: Baseline, 16 weeks, 32 weeks, 48 weeks
Population: Per-protocol set: randomized; no entry criteria violations; completed \>=32 weeks of study; no systemic glucocorticoid therapy \>14 cumulative days during study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Week 32 | 6.62 millimoles per liter (mmol/L) | Standard Deviation 1.55 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Baseline | 10.39 millimoles per liter (mmol/L) | Standard Deviation 2.72 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Week 32 | 8.80 millimoles per liter (mmol/L) | Standard Deviation 2.43 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Week 16 | 9.79 millimoles per liter (mmol/L) | Standard Deviation 2.74 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Week 32 | 6.93 millimoles per liter (mmol/L) | Standard Deviation 2.12 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Baseline | 13.64 millimoles per liter (mmol/L) | Standard Deviation 3.13 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Week 32 | 9.33 millimoles per liter (mmol/L) | Standard Deviation 2.49 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Week 16 | 7.94 millimoles per liter (mmol/L) | Standard Deviation 2.37 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Week 32 | 7.71 millimoles per liter (mmol/L) | Standard Deviation 2.18 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Baseline | 12.59 millimoles per liter (mmol/L) | Standard Deviation 3.09 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Week 32 | 8.62 millimoles per liter (mmol/L) | Standard Deviation 2.26 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Week 16 | 10.13 millimoles per liter (mmol/L) | Standard Deviation 2.63 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Week 32 | 6.63 millimoles per liter (mmol/L) | Standard Deviation 1.75 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Baseline | 12.77 millimoles per liter (mmol/L) | Standard Deviation 2.91 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Week 48 | 6.74 millimoles per liter (mmol/L) | Standard Deviation 1.52 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Week 16 | 8.52 millimoles per liter (mmol/L) | Standard Deviation 2.5 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Week 48 | 8.79 millimoles per liter (mmol/L) | Standard Deviation 2.28 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Baseline | 10.09 millimoles per liter (mmol/L) | Standard Deviation 2.82 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Week 48 | 7.01 millimoles per liter (mmol/L) | Standard Deviation 1.99 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Week 16 | 9.35 millimoles per liter (mmol/L) | Standard Deviation 2.73 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Week 48 | 9.25 millimoles per liter (mmol/L) | Standard Deviation 2.31 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Baseline | 10.36 millimoles per liter (mmol/L) | Standard Deviation 3.22 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Week 48 | 7.33 millimoles per liter (mmol/L) | Standard Deviation 1.86 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Week 16 | 7.15 millimoles per liter (mmol/L) | Standard Deviation 2.09 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Week 48 | 8.74 millimoles per liter (mmol/L) | Standard Deviation 2.11 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Week 16 | 7.04 millimoles per liter (mmol/L) | Standard Deviation 1.84 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Week 48 | 6.53 millimoles per liter (mmol/L) | Standard Deviation 1.54 |
| Insulin Lispro LM | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Baseline | 9.92 millimoles per liter (mmol/L) | Standard Deviation 2.28 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Week 48 | 6.56 millimoles per liter (mmol/L) | Standard Deviation 1.73 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Baseline | 10.04 millimoles per liter (mmol/L) | Standard Deviation 2.36 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Baseline | 13.70 millimoles per liter (mmol/L) | Standard Deviation 3.42 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Baseline | 10.62 millimoles per liter (mmol/L) | Standard Deviation 3.12 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Baseline | 12.70 millimoles per liter (mmol/L) | Standard Deviation 3.36 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Baseline | 10.65 millimoles per liter (mmol/L) | Standard Deviation 3.14 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Baseline | 12.80 millimoles per liter (mmol/L) | Standard Deviation 3.64 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Baseline | 10.12 millimoles per liter (mmol/L) | Standard Deviation 3.03 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Week 16 | 6.55 millimoles per liter (mmol/L) | Standard Deviation 1.67 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Week 16 | 9.55 millimoles per liter (mmol/L) | Standard Deviation 2.79 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Week 16 | 7.64 millimoles per liter (mmol/L) | Standard Deviation 2.33 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Week 16 | 9.58 millimoles per liter (mmol/L) | Standard Deviation 2.65 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Week 16 | 7.81 millimoles per liter (mmol/L) | Standard Deviation 2.46 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Week 16 | 9.80 millimoles per liter (mmol/L) | Standard Deviation 2.9 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Week 16 | 7.01 millimoles per liter (mmol/L) | Standard Deviation 1.96 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Week 32 | 6.21 millimoles per liter (mmol/L) | Standard Deviation 1.19 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Week 32 | 8.73 millimoles per liter (mmol/L) | Standard Deviation 2.09 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Week 32 | 6.90 millimoles per liter (mmol/L) | Standard Deviation 1.76 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Week 32 | 8.86 millimoles per liter (mmol/L) | Standard Deviation 2.14 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Week 32 | 7.50 millimoles per liter (mmol/L) | Standard Deviation 1.92 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Week 32 | 8.96 millimoles per liter (mmol/L) | Standard Deviation 2.31 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | 0300 Hours Week 32 | 6.75 millimoles per liter (mmol/L) | Standard Deviation 1.73 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Pre-Meal Week 48 | 6.37 millimoles per liter (mmol/L) | Standard Deviation 1.17 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Morning Postprandial Meal Week 48 | 8.85 millimoles per liter (mmol/L) | Standard Deviation 2.21 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Pre-Meal Week 48 | 6.99 millimoles per liter (mmol/L) | Standard Deviation 1.79 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Midday Postprandial Meal Week 48 | 8.88 millimoles per liter (mmol/L) | Standard Deviation 2.31 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Pre-Meal Week 48 | 7.33 millimoles per liter (mmol/L) | Standard Deviation 2.03 |
| Insulin Glargine | 7-point Self-monitored Blood Glucose Profiles | Evening Postprandial Meal Week 48 | 8.90 millimoles per liter (mmol/L) | Standard Deviation 2.29 |
Secondary
Change From Baseline in Postprandial Blood Glucose Over Time
The change in blood glucose was evaluated by the GlycoMark™ test. GlycoMark measures levels of 1,5 anhydroglucitol (1,5 AG) in serum or plasma, allowing for the short- to intermediate-term monitoring of glycemic control in patients with diabetes. When 1,5 AG values decrease, serum glucose levels increase.
Time frame: Baseline, 16 weeks, 32 weeks, 48 weeks
Population: Per-protocol set: randomized; no entry criteria violations; completed \>=32 weeks of study; no systemic glucocorticoid therapy \>14 cumulative days during study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro LM | Change From Baseline in Postprandial Blood Glucose Over Time | Week 48 Change from Baseline | 5.24 millimoles per liter | Standard Error 1.2 |
| Insulin Lispro LM | Change From Baseline in Postprandial Blood Glucose Over Time | Week 16 Change from Baseline | 3.32 millimoles per liter | Standard Error 1.16 |
| Insulin Lispro LM | Change From Baseline in Postprandial Blood Glucose Over Time | Week 32 Change from Baseline | 4.69 millimoles per liter | Standard Error 1.19 |
| Insulin Glargine | Change From Baseline in Postprandial Blood Glucose Over Time | Week 48 Change from Baseline | 4.89 millimoles per liter | Standard Error 1.2 |
| Insulin Glargine | Change From Baseline in Postprandial Blood Glucose Over Time | Week 16 Change from Baseline | 3.55 millimoles per liter | Standard Error 1.17 |
| Insulin Glargine | Change From Baseline in Postprandial Blood Glucose Over Time | Week 32 Change from Baseline | 4.56 millimoles per liter | Standard Error 1.18 |
p-value: 0.604Mixed Models Analysis
p-value: 0.814Mixed Models Analysis
p-value: 0.582Mixed Models Analysis
Secondary
Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles
Time frame: baseline, 48 weeks
Population: Full Analysis Set: all randomized participants who received at least one dose of study drug and had baseline and endpoint values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro LM | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | Cholesterol (n=195, n=203) | -0.18 millimoles/Liter (mmol/L) | Standard Error 0.18 |
| Insulin Lispro LM | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | Low Density Lipoprotein (n=178, n=191) | -0.11 millimoles/Liter (mmol/L) | Standard Error 0.17 |
| Insulin Lispro LM | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | High Density Lipoprotein (n=195, n=203) | 0.06 millimoles/Liter (mmol/L) | Standard Error 0.05 |
| Insulin Lispro LM | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | Triglycerides (n=195, n=203) | -0.09 millimoles/Liter (mmol/L) | Standard Error 0.21 |
| Insulin Glargine | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | Low Density Lipoprotein (n=178, n=191) | -0.06 millimoles/Liter (mmol/L) | Standard Error 0.17 |
| Insulin Glargine | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | Cholesterol (n=195, n=203) | -0.08 millimoles/Liter (mmol/L) | Standard Error 0.18 |
| Insulin Glargine | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | Triglycerides (n=195, n=203) | 0.03 millimoles/Liter (mmol/L) | Standard Error 0.21 |
| Insulin Glargine | Change From Baseline to 48 Week Endpoint in Lipid and Cholesterol Profiles | High Density Lipoprotein (n=195, n=203) | 0.04 millimoles/Liter (mmol/L) | Standard Error 0.05 |
p-value: 0.16295% CI: [-0.26, 0.04]ANCOVA
p-value: 0.16595% CI: [-0.3, 0.05]ANCOVA
p-value: 0.5195% CI: [-0.18, 0.09]ANCOVA
p-value: 0.38295% CI: [-0.02, 0.06]ANCOVA
Secondary
Change in Hemoglobin A1c (HbA1c) Over Time
Time frame: Baseline, 16 Weeks, 32 Weeks, 48 Weeks
Population: Per-protocol set: randomized, no entry criteria violations, completed \>=32 weeks of study, and no systemic glucocorticoid therapy for \>14 cumulative days during study.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro LM | Change in Hemoglobin A1c (HbA1c) Over Time | 16 Week Change from Baseline | -1.65 percent (%) glycated hemoglobin | Standard Error 0.23 |
| Insulin Lispro LM | Change in Hemoglobin A1c (HbA1c) Over Time | 32 Week Change from Baseline | -1.92 percent (%) glycated hemoglobin | Standard Error 0.23 |
| Insulin Lispro LM | Change in Hemoglobin A1c (HbA1c) Over Time | 48 Week Change from Baseline | -1.91 percent (%) glycated hemoglobin | Standard Error 0.23 |
| Insulin Glargine | Change in Hemoglobin A1c (HbA1c) Over Time | 16 Week Change from Baseline | -1.76 percent (%) glycated hemoglobin | Standard Error 0.23 |
| Insulin Glargine | Change in Hemoglobin A1c (HbA1c) Over Time | 32 Week Change from Baseline | -1.90 percent (%) glycated hemoglobin | Standard Error 0.23 |
| Insulin Glargine | Change in Hemoglobin A1c (HbA1c) Over Time | 48 Week Change from Baseline | -1.87 percent (%) glycated hemoglobin | Standard Error 0.23 |
p-value: 0.279Mixed Models Analysis
p-value: 0.846Mixed Models Analysis
p-value: 0.741Mixed Models Analysis
Secondary
Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks
Time frame: 16 weeks, 32 weeks, 48 weeks
Population: Full Analysis Set: all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro LM | Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks | Week 16 | 0.49 Units of insulin/kilogram/day (U/kg/day) | Standard Deviation 0.36 |
| Insulin Lispro LM | Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks | Week 32 | 0.65 Units of insulin/kilogram/day (U/kg/day) | Standard Deviation 0.43 |
| Insulin Lispro LM | Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks | Week 48 | 0.71 Units of insulin/kilogram/day (U/kg/day) | Standard Deviation 0.45 |
| Insulin Glargine | Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks | Week 16 | 0.49 Units of insulin/kilogram/day (U/kg/day) | Standard Deviation 0.29 |
| Insulin Glargine | Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks | Week 32 | 0.65 Units of insulin/kilogram/day (U/kg/day) | Standard Deviation 0.42 |
| Insulin Glargine | Daily Total Insulin Dose Per Body Weight (U/kg/Day) at 16, 32, and 48 Weeks | Week 48 | 0.71 Units of insulin/kilogram/day (U/kg/day) | Standard Deviation 0.47 |
Secondary
Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks
Time frame: 16 weeks, 32 weeks, 48 weeks
Population: Full Analysis Set: all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Lispro LM | Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks | Week 16 | 36.42 Units of insulin per day (U/day) | Standard Deviation 25.9 |
| Insulin Lispro LM | Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks | Week 32 | 50.38 Units of insulin per day (U/day) | Standard Deviation 34.02 |
| Insulin Lispro LM | Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks | Week 48 | 54.97 Units of insulin per day (U/day) | Standard Deviation 37.12 |
| Insulin Glargine | Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks | Week 16 | 35.87 Units of insulin per day (U/day) | Standard Deviation 21.55 |
| Insulin Glargine | Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks | Week 32 | 48.16 Units of insulin per day (U/day) | Standard Deviation 31.18 |
| Insulin Glargine | Daily Total Insulin Dose (U/Day) at 16, 32, and 48 Weeks | Week 48 | 54.03 Units of insulin per day (U/day) | Standard Deviation 35.9 |
Secondary
Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time
Time frame: 16 weeks, 32 weeks, 48 weeks
Population: Per-protocol set: randomized; no entry criteria violations; completed \>=32 weeks of study; no systemic glucocorticoid therapy \>14 cumulative days during study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro LM | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 7.0 % at 32 weeks | 40.6 percentage of participants |
| Insulin Lispro LM | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 7.0 % at 48 weeks | 40.0 percentage of participants |
| Insulin Lispro LM | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 6.5 % at 32 weeks | 19.4 percentage of participants |
| Insulin Lispro LM | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 6.5 % at 16 weeks | 10.2 percentage of participants |
| Insulin Lispro LM | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 6.5 % at 48 weeks | 21.2 percentage of participants |
| Insulin Lispro LM | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 7.0 % at 16 weeks | 28.2 percentage of participants |
| Insulin Glargine | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 6.5 % at 48 weeks | 19.0 percentage of participants |
| Insulin Glargine | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 6.5 % at 32 weeks | 17.5 percentage of participants |
| Insulin Glargine | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 7.0 % at 32 weeks | 38.8 percentage of participants |
| Insulin Glargine | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 7.0 % at 16 weeks | 32.6 percentage of participants |
| Insulin Glargine | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 7.0 % at 48 weeks | 39.1 percentage of participants |
| Insulin Glargine | Percentage of Patients Achieving HbA1c <6.5% and <7% Over Time | Percent achieving HbA1c < 6.5 % at 16 weeks | 12.5 percentage of participants |
p-value: 0.46595% CI: [0.41, 1.5]Regression, Logistic
p-value: 0.36595% CI: [0.51, 1.28]Regression, Logistic
p-value: 0.68395% CI: [0.65, 1.95]Regression, Logistic
p-value: 0.8195% CI: [0.68, 1.64]Regression, Logistic
p-value: 0.55595% CI: [0.69, 2.01]Regression, Logistic
p-value: 0.82995% CI: [0.67, 1.64]Regression, Logistic
Secondary
Safety: Number of Participants With Serious and Non-Serious Adverse Events
Safety was assessed via serious adverse events (SAEs) and AEs, the details of which are listed in the Reported Adverse Event section.
Time frame: baseline through 48 weeks
Population: Full Analysis Set: all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Lispro LM | Safety: Number of Participants With Serious and Non-Serious Adverse Events | Serious Adverse Events | 19 participants |
| Insulin Lispro LM | Safety: Number of Participants With Serious and Non-Serious Adverse Events | Non-Serious Adverse Events | 107 participants |
| Insulin Glargine | Safety: Number of Participants With Serious and Non-Serious Adverse Events | Serious Adverse Events | 13 participants |
| Insulin Glargine | Safety: Number of Participants With Serious and Non-Serious Adverse Events | Non-Serious Adverse Events | 116 participants |