Type 1 Diabetes
Conditions
Keywords
Insulin Glargine
Brief summary
The purpose of this study is to compare long-acting basal insulin analog LY2963016 to Lantus® in combination with mealtime insulin lispro in adult Chinese participants with Type 1 Diabetes Mellitus (T1DM).
Interventions
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 T1DM based on the disease diagnostic criteria (World Health Organization \[WHO\] Classification). * Have duration of T1DM ≥1 year. * Have HbA1c ≤11 %. * Have been administered with basal-bolus insulins or pre-mixed insulins for at least 90 days prior to screening. * Have a body mass index (BMI) ≤35 kilograms per meter squared.
Exclusion criteria
* Exposure to an insulin glargine other than Lantus® within previous 30 days. * Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study. * Have had more than one episode of diabetic ketoacidosis or emergency room visits for uncontrolled diabetes leading to hospitalization within 6 months prior to entry into the study. * Have known hypersensitivity or allergy to any of the study insulins (Lantus® or insulin lispro) or to excipients of the study insulins. * Are pregnant, intend to become pregnant during the course of the study. * Women who are breastfeeding. * Are currently taking traditional medicine (herbal medicine or patent medicine) with known/specified content of anti-hyperglycemic effects within 3 months before screening. * Have congestive heart failure Class III and IV. * Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease. * Have any active cancer. * Have a history or diagnosis of human immunodeficiency virus (HIV) infection. * Have presence of clinically significant gastrointestinal disease. * Have a history of renal transplantation, or are currently receiving renal dialysis. * Are receiving chronic systemic glucocorticoid therapy at pharmacological doses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®) | Baseline, Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated using mixed-effects model for repeated measures (MMRM) with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time\*Treatment (Type III sum of squares). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Baseline, Week 24 | The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Before Morning Meal Glucose, 2 Hours After Morning Meal Glucose, Before Mid-Day Meal Glucose, 2 Hours After Mid-Day Meal Glucose, Before Evening Meal Glucose, Bedtime Glucose and 0300 Am Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Percentage of Participants With HbA1c <7% | Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Percentage of Participants With HbA1c ≤6.5% | Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG | Baseline, Week 24 | Change From Baseline in Intrapatient blood glucose (BG). LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in Glycemic Variability of Fasting Blood Glucose | Baseline, Week 24 | Change From Baseline in Glycemic Variability of Fasting Blood Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). |
| Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016) | Baseline, Week 24 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was calculated using MMRM with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time\*Treatment (Type III sum of squares). |
| Change From Baseline in Prandial Insulin Dose | Baseline, Week 24 | Prandial Insulin Dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured. |
| Change From Baseline in Body Weight | Baseline, Week 24 | Change from baseline in body weight. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured. |
| Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | Baseline, Week 24 | The ITSQ is a validated 22-item questionnaire that was used to assess treatment satisfaction. Items were measured on a 7-point scale, with lower scores reflecting better outcomes. In addition to an overall score, scores were also obtained for 5 domains, including inconvenience of regimen, lifestyle flexibility, glycemic control, hypoglycemic control, and insulin delivery device. Raw domain and overall scores were transformed on a scale from 0 to 100, where a higher score indicated better treatment satisfaction. LS mean was calculated using ANCOVA with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment (Type III sum of squares). |
| Number of Participants With Detectable Anti-Glargine Antibodies | Baseline through Week 24 | Number of participants with detectable anti-glargine antibodies |
| Rate of Documented Symptomatic Hypoglycemia | Baseline through Week 24 | Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). The overall yearly rates (events/participant/year) of those hypoglycemic events, calculated as, for each participant, the number of episodes times 365.25 and then divided by the participants treatment duration, will be summarized, and analyzed by a Negative-binomial regression model with treatment as fixed effects and log of (patient's treatment duration/365.25) as an offset variable. |
| Change From Baseline in Basal Insulin Dose | Baseline, Week 24 | Change from baseline in basal insulin dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2963016 + Insulin Lispro Participants received 100 units per milliliter (U/mL) LY2963016 administered subcutaneously (SC) once daily (QD) and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | 137 |
| Lantus® + Insulin Lispro Participants received 100 U/mL Lantus® administered SC QD and 100 U/mL premeal insulin lispro administered SC thrice-daily (TID) within 15 minutes before meals or immediately after the meal. | 135 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Protocol Violation | 3 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | LY2963016 + Insulin Lispro | Lantus® + Insulin Lispro | Total |
|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 15 | 41.4 years STANDARD_DEVIATION 13.8 | 41.6 years STANDARD_DEVIATION 14.4 |
| Body Mass Index (BMI) | 21.90 kilogram per meter square (kg/m²) STANDARD_DEVIATION 2.54 | 22.03 kilogram per meter square (kg/m²) STANDARD_DEVIATION 2.32 | 21.96 kilogram per meter square (kg/m²) STANDARD_DEVIATION 2.43 |
| Duration of Diabetes in years | 10.29 years STANDARD_DEVIATION 9.53 | 10.53 years STANDARD_DEVIATION 9.53 | 10.41 years STANDARD_DEVIATION 9.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 137 Participants | 135 Participants | 272 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1c (HbA1c) at Baseline | 7.90 Percentage of HbA1c STANDARD_DEVIATION 1.32 | 7.85 Percentage of HbA1c STANDARD_DEVIATION 1.48 | 7.88 Percentage of HbA1c STANDARD_DEVIATION 1.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 137 Participants | 135 Participants | 272 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 137 Participants | 135 Participants | 272 Participants |
| Sex: Female, Male Female | 77 Participants | 66 Participants | 143 Participants |
| Sex: Female, Male Male | 60 Participants | 69 Participants | 129 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 137 | 0 / 135 |
| other Total, other adverse events | 84 / 137 | 77 / 135 |
| serious Total, serious adverse events | 9 / 137 | 8 / 135 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®)
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean was calculated using mixed-effects model for repeated measures (MMRM) with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time\*Treatment (Type III sum of squares).
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®) | -0.20 Percentage of HbA1c | Standard Error 0.071 |
| Lantus® + Insulin Lispro | Change From Baseline in Hemoglobin A1c (HbA1c) (LY2963016 Noninferior to Lantus®) | -0.08 Percentage of HbA1c | Standard Error 0.071 |
95% CI: [-0.32, 0.08]
Secondary
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values
The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Before Morning Meal Glucose, 2 Hours After Morning Meal Glucose, Before Mid-Day Meal Glucose, 2 Hours After Mid-Day Meal Glucose, Before Evening Meal Glucose, Bedtime Glucose and 0300 Am Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline SMBG value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Before Morning Meal Glucose | -7.2 milligrams per deciliter (mg/dL) | Standard Error 3.64 |
| LY2963016 + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | 2 Hours After Morning Meal Glucose | -10.6 milligrams per deciliter (mg/dL) | Standard Error 4.77 |
| LY2963016 + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Before Mid-Day Meal Glucose | -4.6 milligrams per deciliter (mg/dL) | Standard Error 4.13 |
| LY2963016 + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | 2 Hours After Mid-Day Meal Glucose | -1.6 milligrams per deciliter (mg/dL) | Standard Error 4.76 |
| LY2963016 + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Before Evening Meal Glucose | -6.2 milligrams per deciliter (mg/dL) | Standard Error 4.78 |
| LY2963016 + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Bedtime Glucose | -0.4 milligrams per deciliter (mg/dL) | Standard Error 4.99 |
| LY2963016 + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | 0300 Am Glucose | -4.9 milligrams per deciliter (mg/dL) | Standard Error 3.87 |
| Lantus® + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | 2 Hours After Morning Meal Glucose | -2.8 milligrams per deciliter (mg/dL) | Standard Error 4.83 |
| Lantus® + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Bedtime Glucose | 5.0 milligrams per deciliter (mg/dL) | Standard Error 5.06 |
| Lantus® + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Before Evening Meal Glucose | 4.8 milligrams per deciliter (mg/dL) | Standard Error 4.85 |
| Lantus® + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Before Mid-Day Meal Glucose | 8.5 milligrams per deciliter (mg/dL) | Standard Error 4.21 |
| Lantus® + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | 0300 Am Glucose | 2.5 milligrams per deciliter (mg/dL) | Standard Error 3.94 |
| Lantus® + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | 2 Hours After Mid-Day Meal Glucose | 1.9 milligrams per deciliter (mg/dL) | Standard Error 4.76 |
| Lantus® + Insulin Lispro | Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values | Before Morning Meal Glucose | -0.4 milligrams per deciliter (mg/dL) | Standard Error 3.68 |
Comparison: Before Morning Meal Glucosep-value: 0.19195% CI: [-17, 3.4]Mixed Models Analysis
Comparison: 2 Hours After Morning Meal Glucosep-value: 0.2595% CI: [-21.2, 5.5]Mixed Models Analysis
Comparison: Before Mid-Day Meal Glucosep-value: 0.02895% CI: [-24.7, -1.5]Mixed Models Analysis
Comparison: 2 Hours After Mid-Day Meal Glucosep-value: 0.59995% CI: [-16.8, 9.7]Mixed Models Analysis
Comparison: Before Evening Meal Glucosep-value: 0.10995% CI: [-24.4, 2.5]Mixed Models Analysis
Comparison: Bedtime Glucosep-value: 0.45295% CI: [-19.4, 8.6]Mixed Models Analysis
Comparison: 0300 Am Glucosep-value: 0.1895% CI: [-18.3, 3.5]Mixed Models Analysis
Secondary
Change From Baseline in Basal Insulin Dose
Change from baseline in basal insulin dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline Basal Insulin dose value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in Basal Insulin Dose | 0.7 Units per Day (U/day) | Standard Error 0.33 |
| Lantus® + Insulin Lispro | Change From Baseline in Basal Insulin Dose | 1.5 Units per Day (U/day) | Standard Error 0.33 |
p-value: 0.0995% CI: [-1.7, 0.1]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
Change from baseline in body weight. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline weight value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in Body Weight | 0.8 kilograms (kg) | Standard Error 0.21 |
| Lantus® + Insulin Lispro | Change From Baseline in Body Weight | 0.9 kilograms (kg) | Standard Error 0.22 |
p-value: 0.7795% CI: [-0.7, 0.5]Mixed Models Analysis
Secondary
Change From Baseline in Glycemic Variability of Fasting Blood Glucose
Change From Baseline in Glycemic Variability of Fasting Blood Glucose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline SMBG value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in Glycemic Variability of Fasting Blood Glucose | Daily Mean Standard Deviation | -10.4 mg/dL | Standard Error 1.69 |
| LY2963016 + Insulin Lispro | Change From Baseline in Glycemic Variability of Fasting Blood Glucose | Morning Pre-meal Standard Deviation | -9.0 mg/dL | Standard Error 2.53 |
| Lantus® + Insulin Lispro | Change From Baseline in Glycemic Variability of Fasting Blood Glucose | Morning Pre-meal Standard Deviation | -5.5 mg/dL | Standard Error 2.56 |
| Lantus® + Insulin Lispro | Change From Baseline in Glycemic Variability of Fasting Blood Glucose | Daily Mean Standard Deviation | -8.6 mg/dL | Standard Error 1.71 |
Comparison: Morning Pre-meal Standard Deviationp-value: 0.32895% CI: [-10.6, 3.6]Mixed Models Analysis
Comparison: Daily Mean Standard Deviationp-value: 0.46795% CI: [-6.5, 3]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016)
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean was calculated using MMRM with variables baseline HbA1c + Treatment + Pre-study treatment + Pre-study metformin or acarbose usage + Time + Time\*Treatment (Type III sum of squares).
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline HbA1c value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016) | -0.20 Percentage of HbA1c | Standard Error 0.071 |
| Lantus® + Insulin Lispro | Change From Baseline in HbA1c (Lantus® Noninferior to LY2963016) | -0.08 Percentage of HbA1c | Standard Error 0.071 |
95% CI: [-0.32, 0.08]
Secondary
Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ)
The ITSQ is a validated 22-item questionnaire that was used to assess treatment satisfaction. Items were measured on a 7-point scale, with lower scores reflecting better outcomes. In addition to an overall score, scores were also obtained for 5 domains, including inconvenience of regimen, lifestyle flexibility, glycemic control, hypoglycemic control, and insulin delivery device. Raw domain and overall scores were transformed on a scale from 0 to 100, where a higher score indicated better treatment satisfaction. LS mean was calculated using ANCOVA with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment (Type III sum of squares).
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline ITSQ score.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Hypoglycemic Control Transformed Score | 3.2 score on a scale | Standard Error 1.39 |
| LY2963016 + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Lifestyle Flexibility Transformed Score | 1.3 score on a scale | Standard Error 1.86 |
| LY2963016 + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Glycemic Control Transformed Score | 6.9 score on a scale | Standard Error 1.64 |
| LY2963016 + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Insulin Delivery Device Satisfaction Transformed Score | 3.3 score on a scale | Standard Error 1.26 |
| LY2963016 + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Total Transformed Score | 3.3 score on a scale | Standard Error 1.1 |
| LY2963016 + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Inconvenience of Regimen Transformed Score | 3.5 score on a scale | Standard Error 1.3 |
| Lantus® + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Total Transformed Score | 4.1 score on a scale | Standard Error 1.1 |
| Lantus® + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Insulin Delivery Device Satisfaction Transformed Score | 2.9 score on a scale | Standard Error 1.26 |
| Lantus® + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Lifestyle Flexibility Transformed Score | 2.0 score on a scale | Standard Error 1.86 |
| Lantus® + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Hypoglycemic Control Transformed Score | 3.8 score on a scale | Standard Error 1.38 |
| Lantus® + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Inconvenience of Regimen Transformed Score | 3.8 score on a scale | Standard Error 1.29 |
| Lantus® + Insulin Lispro | Change From Baseline in Insulin Treatment Satisfaction Questionnaire (ITSQ) | ITSQ Glycemic Control Transformed Score | 6.0 score on a scale | Standard Error 1.64 |
Comparison: ITSQ Inconvenience of Regimen Transformed Scorep-value: 0.87995% CI: [-3.9, 3.3]ANCOVA
Comparison: ITSQ Lifestyle Flexibility Transformed Scorep-value: 0.78895% CI: [-5.9, 4.5]ANCOVA
Comparison: ITSQ Hypoglycemic Control Transformed Scorep-value: 0.77595% CI: [-4.5, 3.3]ANCOVA
Comparison: ITSQ Glycemic Control Transformed Scorep-value: 0.68195% CI: [-3.6, 5.6]ANCOVA
Comparison: ITSQ Insulin Delivery Device Satisfaction Transformed Scorep-value: 0.81995% CI: [-3.1, 3.9]ANCOVA
Comparison: ITSQ Total Transformed Scorep-value: 0.60595% CI: [-3.9, 2.3]ANCOVA
Secondary
Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG
Change From Baseline in Intrapatient blood glucose (BG). LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares).
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline SMBG value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG | -2.9 mg/dL | Standard Error 1.33 |
| Lantus® + Insulin Lispro | Change From Baseline in Intrapatient Blood Glucose (BG) Variability, Measured by the Standard Deviation of 7-point SMBG | -2.6 mg/dL | Standard Error 1.34 |
p-value: 0.88595% CI: [-0.4, 3.4]Mixed Models Analysis
Secondary
Change From Baseline in Prandial Insulin Dose
Prandial Insulin Dose. LS mean was calculated using MMRM with variables Baseline + Pre-study Treatment + Pre-study Metformin or Acarbose Usage + HbA1c at Baseline + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Measurement) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.
Time frame: Baseline, Week 24
Population: All randomized participants who received at least one dose of study drug and had a baseline and postbaseline Prandial Insulin dose value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Change From Baseline in Prandial Insulin Dose | 0.2 U/day | Standard Error 0.49 |
| Lantus® + Insulin Lispro | Change From Baseline in Prandial Insulin Dose | 1.4 U/day | Standard Error 0.5 |
p-value: 0.08995% CI: [-2.6, 0.2]Mixed Models Analysis
Secondary
Number of Participants With Detectable Anti-Glargine Antibodies
Number of participants with detectable anti-glargine antibodies
Time frame: Baseline through Week 24
Population: All participants who received at least one dose of study drug.Only participants with detected or non-detected insulin antibody levels at baseline and post-baseline were included in analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Number of Participants With Detectable Anti-Glargine Antibodies | Detectable Anti-Glargine Antibodies | 76 Participants |
| LY2963016 + Insulin Lispro | Number of Participants With Detectable Anti-Glargine Antibodies | Detectable Cross Reactive Insulin Antibodies | 67 Participants |
| LY2963016 + Insulin Lispro | Number of Participants With Detectable Anti-Glargine Antibodies | Treatment Emergent Antibody Response (TEAR) | 42 Participants |
| Lantus® + Insulin Lispro | Number of Participants With Detectable Anti-Glargine Antibodies | Detectable Anti-Glargine Antibodies | 68 Participants |
| Lantus® + Insulin Lispro | Number of Participants With Detectable Anti-Glargine Antibodies | Detectable Cross Reactive Insulin Antibodies | 58 Participants |
| Lantus® + Insulin Lispro | Number of Participants With Detectable Anti-Glargine Antibodies | Treatment Emergent Antibody Response (TEAR) | 35 Participants |
Secondary
Percentage of Participants With HbA1c ≤6.5%
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time frame: Week 24
Population: All randomized participants who received at least one dose of study drug and had baseline and postbaseline HbA1c value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2963016 + Insulin Lispro | Percentage of Participants With HbA1c ≤6.5% | 15.7 percentage of participants |
| Lantus® + Insulin Lispro | Percentage of Participants With HbA1c ≤6.5% | 22.4 percentage of participants |
p-value: 0.201Fisher Exact
Secondary
Percentage of Participants With HbA1c <7%
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time frame: Week 24
Population: All randomized participants who received at least one dose of study drug and had baseline and postbaseline HbA1c value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2963016 + Insulin Lispro | Percentage of Participants With HbA1c <7% | 30.7 percentage of participants |
| Lantus® + Insulin Lispro | Percentage of Participants With HbA1c <7% | 32.8 percentage of participants |
p-value: 0.787Fisher Exact
Secondary
Rate of Documented Symptomatic Hypoglycemia
Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). The overall yearly rates (events/participant/year) of those hypoglycemic events, calculated as, for each participant, the number of episodes times 365.25 and then divided by the participants treatment duration, will be summarized, and analyzed by a Negative-binomial regression model with treatment as fixed effects and log of (patient's treatment duration/365.25) as an offset variable.
Time frame: Baseline through Week 24
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2963016 + Insulin Lispro | Rate of Documented Symptomatic Hypoglycemia | 12.6 events/participant/year | Standard Error 2.42 |
| Lantus® + Insulin Lispro | Rate of Documented Symptomatic Hypoglycemia | 14.0 events/participant/year | Standard Error 2.64 |