Diabetes Mellitus, Type 2
Conditions
Brief summary
Comparison of fasting blood glucose levels in patients with Type 2 diabetes after 12 weeks of treatment with a new basal insulin analog or with insulin glargine.
Detailed description
Patients in this study will continue to use their stable prestudy dose of metformin and/or a sulfonylurea. Prestudy therapy also includes once daily insulin glargine or neutral protamine Hagedorn (NPH) insulin. The 12-week active treatment phase will be followed by a 4-week follow-up period, during which patients will return to the basal insulin recommended by the investigator.
Interventions
DRUGLY2605541
subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
DRUGinsulin glargine
subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 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
* Type 2 diabetes mellitus (T2DM) for at least 1 year * At least 18 years of age * Using metformin and/or sulfonylurea(s) with once daily glargine or NPH for at least 3 months prior to the study. Prestudy dose requirements: insulin dose maximum 1.0 unit/kilogram/day (U/kg/day). Oral antihyperglycemic medications (OAMs): Metformin dose at least 1500 milligram/day (mg/day) and/or sulfonylurea dose at least half the maximum daily dose specified in the local package insert. OAM doses stable for 6 weeks prior to the study. * Hemoglobin A1c (HbA1c) less than or equal to 10.5% before randomization * Body Mass Index (BMI) 19 to 45 kilogram/square meter (kg/m²) * Capable and willing to prepare and inject insulin with a syringe while continuing to use the prestudy OAMs, monitor own blood glucose; complete the study diary; be receptive to diabetes education; comply with study visits and receive telephone calls between visits * Women of childbearing potential must test negative for pregnancy before receiving treatment and agree to use reliable birth control until completing the follow-up visit
Exclusion criteria
* Long-term use of short- or rapid-acting or premixed insulin within the 6 months before the study. Short-term insulin therapy or occasional use are permitted * Use of any glucose-lowering medications not allowed by the inclusion criteria in the 3 months before entry into the study * Use of prescription or over-the-counter medications to promote weight loss within 3 months before entry into the study * Current participation in a weight loss program, or plans to do so during the study * Treatment with any antibody-based therapy within 6 months prior to the study * Use of chronic (\>14 consecutive days) systemic glucocorticoid therapy currently or within 4 weeks prior to the study * More than 1 episode of severe hypoglycemia within 6 months prior to the study, or currently diagnosed with hypoglycemia unawareness * 2 or more emergency room visits or hospitalizations due to poor glucose control in the 6 months preceding the study * Liver disease * History of renal transplantation, current renal dialysis, or creatinine \>2.0 milligram/deciliter (mg/dL) (177 micromole/Liter \[μmol\]/L) * Cardiac disease with a marked impact on physical functioning * Clinically significant electrocardiogram (ECG) abnormalities at screening * Malignancy other than basal cell or squamous cell skin cancer * Fasting triglycerides \>500 mg/dL * Known diabetic autonomic neuropathy * Known hypersensitivity or allergy to study insulin or its excipients * Blood transfusion or severe blood loss within 3 months prior to entry into the study or known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c methodology * Irregular sleep/wake cycle * Women who are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | Week 12 | 8-point SMBG profiles are measured at morning FBG, midday and evening pre-meal blood glucose (BG), 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. Least squares (LS) mean of the FBG is from mixed-model repeated measures (MMRM) approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline hemoglobin A1c \[HbA1c\] group); visit; visit and treatment interaction; random effect for participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint | Baseline, Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 dose algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant. |
| Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint | Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment | Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole/Liter (mmol/L) (≤70 milligram/deciliter \[mg/dL\]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). |
| 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Week 12 | 8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant. |
| Daily Basal Insulin Dose at Week 2 and Week 12 | Week 2 and Week 12 | LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant. |
| Percentage of Participants With Hypoglycemia From Baseline Through Week 12 | Baseline through Week 12 | Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). |
| Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 | Baseline through Week 12 | Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30. |
| Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 12 and Week 16 | Negative is defined as either 'negative' from lab or percent binding \<1.16%. Positive is defined as the percent binding is ≥1.16%. The antibody status change is from negative to positive or positive to negative. |
| Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 | Baseline and Week12 | Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant. |
| Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint | Baseline, Week 12 | FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and random effect for participant. |
| Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline, Week 12 | FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant. |
| Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline, Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant. |
| Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. |
| Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). |
| 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | 8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant. |
| Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 2 and Week 12 | LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant. |
| Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline through Week 12 | Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). |
| Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline through Week 12 | Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30. |
| Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline and Week 12 | Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant. |
| Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 12 Endpoint | Week 12 | The drug (LY2605541) concentration at steady state (Css) is calculated from the clearance (Liter/hour) and the final dose of the participants. Clearance was estimated using population-based approaches. |
Countries
Australia, Hungary, Poland, Puerto Rico, Romania, Russia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Insulin Glargine Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks | 93 |
| LY2605541 Algorithm 1 Participants took both LY2605541 and their pre-study insulin for first several days | 98 |
| LY2605541 Algrithm 2 Participants took only LY2605541 with first dose doubled | 97 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 2 |
| Overall Study | Discontinued Prior to Treatment | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 5 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 2 |
| Overall Study | Sponsor Decision | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | Insulin Glargine | LY2605541 Algorithm 1 | LY2605541 Algrithm 2 | Total |
|---|---|---|---|---|
| Age, Continuous | 60.74 years STANDARD_DEVIATION 7.94 | 58.57 years STANDARD_DEVIATION 9.99 | 59.23 years STANDARD_DEVIATION 9.28 | 59.49 years STANDARD_DEVIATION 9.14 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 2 Participants | 6 Participants | 12 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 87 Participants | 0 Participants | 0 Participants | 87 Participants |
| Region of Enrollment Australia | 10 Participants | 5 Participants | 6 Participants | 21 Participants |
| Region of Enrollment Hungary | 5 Participants | 5 Participants | 6 Participants | 16 Participants |
| Region of Enrollment Poland | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment Puerto Rico | 12 Participants | 8 Participants | 9 Participants | 29 Participants |
| Region of Enrollment Romania | 12 Participants | 13 Participants | 12 Participants | 37 Participants |
| Region of Enrollment Russia | 18 Participants | 13 Participants | 12 Participants | 43 Participants |
| Region of Enrollment Spain | 13 Participants | 11 Participants | 12 Participants | 36 Participants |
| Region of Enrollment United States | 23 Participants | 31 Participants | 37 Participants | 91 Participants |
| Sex: Female, Male Female | 46 Participants | 41 Participants | 48 Participants | 135 Participants |
| Sex: Female, Male Male | 47 Participants | 57 Participants | 49 Participants | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 98 | 47 / 98 | 45 / 93 |
| serious Total, serious adverse events | 4 / 98 | 1 / 98 | 2 / 93 |
Outcome results
Primary
Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles
8-point SMBG profiles are measured at morning FBG, midday and evening pre-meal blood glucose (BG), 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. Least squares (LS) mean of the FBG is from mixed-model repeated measures (MMRM) approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline hemoglobin A1c \[HbA1c\] group); visit; visit and treatment interaction; random effect for participant.
Time frame: Week 12
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | 6.83 millimoles per Liter (mmol/L) | Standard Error 0.22 |
| LY2605541 Algorithm 1 | Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | 7.15 millimoles per Liter (mmol/L) | Standard Error 0.22 |
| LY2605541 Algorithm 2 | Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles | 6.84 millimoles per Liter (mmol/L) | Standard Error 0.22 |
p-value: 0.43390% CI: [-0.18, 0.52]Mixed Models Analysis
Secondary
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time frame: Week 12
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Midday Pre-meal BG | 7.47 mmol/L | Standard Error 0.28 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Evening 2-hr postprandial BG | 9.99 mmol/L | Standard Error 0.3 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Midday 2-hr postprandial BG | 9.49 mmol/L | Standard Error 0.28 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Bed time BG | 9.44 mmol/L | Standard Error 0.31 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Morning 2-hr postprandial BG | 9.54 mmol/L | Standard Error 0.31 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | 0300 hours BG | 7.26 mmol/L | Standard Error 0.25 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Evening Pre-meal BG | 7.92 mmol/L | Standard Error 0.28 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | 0300 hours BG | 7.36 mmol/L | Standard Error 0.2 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Morning 2-hr postprandial BG | 9.11 mmol/L | Standard Error 0.25 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Midday 2-hr postprandial BG | 9.22 mmol/L | Standard Error 0.22 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Evening Pre-meal BG | 7.80 mmol/L | Standard Error 0.22 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Evening 2-hr postprandial BG | 9.74 mmol/L | Standard Error 0.24 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Bed time BG | 9.15 mmol/L | Standard Error 0.25 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint | Midday Pre-meal BG | 7.23 mmol/L | Standard Error 0.23 |
p-value: 0.33990% CI: [-0.79, 0.21]Mixed Models Analysis
p-value: 0.67690% CI: [-0.3, 0.5]Mixed Models Analysis
p-value: 0.14490% CI: [-0.92, 0.05]Mixed Models Analysis
p-value: 0.3690% CI: [-0.7, 0.2]Mixed Models Analysis
p-value: 0.34290% CI: [-0.72, 0.19]Mixed Models Analysis
p-value: 0.65490% CI: [-0.56, 0.32]Mixed Models Analysis
p-value: 0.38790% CI: [-0.73, 0.23]Mixed Models Analysis
Secondary
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time frame: Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Morning 2-hr postprandial BG | 9.31 nmol/L | Standard Error 0.27 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Evening Pre-meal BG | 7.79 nmol/L | Standard Error 0.25 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Morning pre-meal BG | 6.76 nmol/L | Standard Error 0.19 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Midday 2-hr postprandial BG | 9.36 nmol/L | Standard Error 0.25 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | 0300 hours BG | 7.10 nmol/L | Standard Error 0.22 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Bed time BG | 9.13 nmol/L | Standard Error 0.27 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Midday Pre-meal BG | 7.29 nmol/L | Standard Error 0.26 |
| Insulin Glargine | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Evening 2-hr postprandial BG | 9.64 nmol/L | Standard Error 0.26 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Midday 2-hr postprandial BG | 8.96 nmol/L | Standard Error 0.27 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Midday Pre-meal BG | 7.22 nmol/L | Standard Error 0.27 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Morning pre-meal BG | 7.02 nmol/L | Standard Error 0.21 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Morning 2-hr postprandial BG | 9.05 nmol/L | Standard Error 0.29 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Evening Pre-meal BG | 7.64 nmol/L | Standard Error 0.27 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Evening 2-hr postprandial BG | 9.14 nmol/L | Standard Error 0.28 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Bed time BG | 8.86 nmol/L | Standard Error 0.29 |
| LY2605541 Algorithm 1 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | 0300 hours BG | 7.34 nmol/L | Standard Error 0.24 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Midday 2-hr postprandial BG | 9.09 nmol/L | Standard Error 0.26 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Evening 2-hr postprandial BG | 9.22 nmol/L | Standard Error 0.27 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Evening Pre-meal BG | 7.64 nmol/L | Standard Error 0.25 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | 0300 hours BG | 6.82 nmol/L | Standard Error 0.23 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Midday Pre-meal BG | 6.60 nmol/L | Standard Error 0.26 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Morning 2-hr postprandial BG | 8.48 nmol/L | Standard Error 0.28 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Bed time BG | 8.43 nmol/L | Standard Error 0.28 |
| LY2605541 Algorithm 2 | 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | Morning pre-meal BG | 6.62 nmol/L | Standard Error 0.2 |
p-value: 0.30590% CI: [-0.16, 0.67]Mixed Models Analysis
p-value: 0.57190% CI: [-0.54, 0.26]Mixed Models Analysis
p-value: 0.45490% CI: [-0.85, 0.32]Mixed Models Analysis
p-value: 0.01690% CI: [-1.4, -0.26]Mixed Models Analysis
p-value: 0.83890% CI: [-0.61, 0.48]Mixed Models Analysis
p-value: 0.03390% CI: [-1.22, -0.16]Mixed Models Analysis
p-value: 0.22990% CI: [-0.95, 0.15]Mixed Models Analysis
p-value: 0.41290% CI: [-0.8, 0.27]Mixed Models Analysis
p-value: 0.64290% CI: [-0.68, 0.38]Mixed Models Analysis
p-value: 0.61490% CI: [-0.67, 0.36]Mixed Models Analysis
p-value: 0.14790% CI: [-1.07, 0.07]Mixed Models Analysis
p-value: 0.2190% CI: [-0.98, 0.13]Mixed Models Analysis
p-value: 0.43890% CI: [-0.86, 0.31]Mixed Models Analysis
p-value: 0.04390% CI: [-1.28, -0.13]Mixed Models Analysis
p-value: 0.40390% CI: [-0.23, 0.72]Mixed Models Analysis
p-value: 0.31490% CI: [-0.75, 0.18]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint
FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and random effect for participant.
Time frame: Baseline, Week 12
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint | -1.77 mmol/Liter | Standard Error 0.26 |
| LY2605541 Algorithm 1 | Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint | -1.97 mmol/Liter | Standard Error 0.21 |
p-value: 0.38890% CI: [-0.59, 0.19]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time frame: Baseline, Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | -1.82 nmol/L | Standard Error 0.23 |
| LY2605541 Algorithm 1 | Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | -2.22 nmol/L | Standard Error 0.24 |
| LY2605541 Algorithm 2 | Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | -1.99 nmol/L | Standard Error 0.23 |
p-value: 0.15990% CI: [-0.87, 0.07]Mixed Models Analysis
p-value: 0.54290% CI: [-0.62, 0.29]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.
Time frame: Baseline, Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | -0.65 percentage of glycated hemoglobin | Standard Error 0.07 |
| LY2605541 Algorithm 1 | Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | -0.67 percentage of glycated hemoglobin | Standard Error 0.07 |
| LY2605541 Algorithm 2 | Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | -0.83 percentage of glycated hemoglobin | Standard Error 0.07 |
p-value: 0.8890% CI: [-0.16, 0.13]Mixed Models Analysis
p-value: 0.04590% CI: [-0.32, -0.03]Mixed Models Analysis
Secondary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 dose algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.
Time frame: Baseline, Week 12
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint | -0.64 percentage of glycated hemoglobin | Standard Error 0.08 |
| LY2605541 Algorithm 1 | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint | -0.74 percentage of glycated hemoglobin | Standard Error 0.06 |
p-value: 0.19790% CI: [-0.21, 0.03]Mixed Models Analysis
Secondary
Daily Basal Insulin Dose at Week 2 and Week 12
LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time frame: Week 2 and Week 12
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Daily Basal Insulin Dose at Week 2 and Week 12 | Week 2 | 2.45 nanomole per kilogram (nmol/kg) | Standard Error 0.15 |
| Insulin Glargine | Daily Basal Insulin Dose at Week 2 and Week 12 | Week 12 | 2.90 nanomole per kilogram (nmol/kg) | Standard Error 0.19 |
| LY2605541 Algorithm 1 | Daily Basal Insulin Dose at Week 2 and Week 12 | Week 2 | 3.19 nanomole per kilogram (nmol/kg) | Standard Error 0.12 |
| LY2605541 Algorithm 1 | Daily Basal Insulin Dose at Week 2 and Week 12 | Week 12 | 4.58 nanomole per kilogram (nmol/kg) | Standard Error 0.15 |
Secondary
Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time frame: Week 2 and Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 2 | 2.62 nmol/kg | Standard Error 0.13 |
| Insulin Glargine | Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | 3.15 nmol/kg | Standard Error 0.16 |
| LY2605541 Algorithm 1 | Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 2 | 3.23 nmol/kg | Standard Error 0.13 |
| LY2605541 Algorithm 1 | Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | 4.58 nmol/kg | Standard Error 0.17 |
| LY2605541 Algorithm 2 | Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 2 | 3.64 nmol/kg | Standard Error 0.13 |
| LY2605541 Algorithm 2 | Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | 5.26 nmol/kg | Standard Error 0.17 |
Secondary
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12
Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time frame: Baseline and Week12
Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 | Baseline | 1.52 nmol/L | Standard Error 0.11 |
| Insulin Glargine | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 | Week 12 | 1.23 nmol/L | Standard Error 0.08 |
| LY2605541 Algorithm 1 | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 | Baseline | 1.51 nmol/L | Standard Error 0.09 |
| LY2605541 Algorithm 1 | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 | Week 12 | 1.20 nmol/L | Standard Error 0.06 |
p-value: 0.93790% CI: [-0.16, 0.14]ANOVA
p-value: 0.68790% CI: [-0.16, 0.1]Mixed Models Analysis
Secondary
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant.
Time frame: Baseline and Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline | 1.43 nmol/L | Standard Error 0.07 |
| Insulin Glargine | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | 1.17 nmol/L | Standard Error 0.07 |
| LY2605541 Algorithm 1 | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline | 1.40 nmol/L | Standard Error 0.08 |
| LY2605541 Algorithm 1 | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | 1.16 nmol/L | Standard Error 0.08 |
| LY2605541 Algorithm 2 | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Baseline | 1.42 nmol/L | Standard Error 0.07 |
| LY2605541 Algorithm 2 | Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | Week 12 | 1.07 nmol/L | Standard Error 0.07 |
p-value: 0.93890% CI: [-0.2, 0.18]ANOVA
p-value: 0.97290% CI: [-0.18, 0.19]ANOVA
p-value: 0.92790% CI: [-0.16, 0.15]Mixed Models Analysis
p-value: 0.29390% CI: [-0.25, 0.05]Mixed Models Analysis
Secondary
Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).
Time frame: Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c ≤6.5% | 6.52 percentage of participants |
| Insulin Glargine | Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c <7.0% | 11.96 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c <7.0% | 21.33 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c ≤6.5% | 9.33 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c <7.0% | 15.66 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c ≤6.5% | 7.23 percentage of participants |
p-value: 0.139Fisher Exact
p-value: 0.569Fisher Exact
p-value: 0.515Fisher Exact
p-value: 1Fisher Exact
Secondary
Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16
Negative is defined as either 'negative' from lab or percent binding \<1.16%. Positive is defined as the percent binding is ≥1.16%. The antibody status change is from negative to positive or positive to negative.
Time frame: Week 12 and Week 16
Population: All randomized participants who took at least one dose of study drug with both baseline and endpoint antibody measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 12 from negative to positive | 2.4 percentage of participants |
| Insulin Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 12 from positive to negative | 2.4 percentage of participants |
| Insulin Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 16 from negative to positive | 2.4 percentage of participants |
| Insulin Glargine | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 16 from positive to negative | 2.4 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 16 from positive to negative | 0.0 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 12 from negative to positive | 4.7 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 16 from negative to positive | 4.9 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 12 from positive to negative | 0.0 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 16 from positive to negative | 1.2 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 12 from positive to negative | 1.1 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 16 from negative to positive | 3.5 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 | Week 12 from negative to positive | 2.8 percentage of participants |
Secondary
Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time frame: Week 12
Population: All randomized participants who took at least one dose of study drug, last observation carried forward (LOCF). Arms are combined due to
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint | HbA1c <7.0% | 48.4 percentage of participants |
| Insulin Glargine | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint | HbA1c ≤6.5% | 23.1 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint | HbA1c <7.0% | 51.9 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint | HbA1c ≤6.5% | 29.5 percentage of participants |
p-value: 0.609Fisher Exact
p-value: 0.314Fisher Exact
Secondary
Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time frame: Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c <7.0% | 48.4 percentage of participants |
| Insulin Glargine | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c ≤6.5% | 23.1 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c <7.0% | 57.5 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c ≤6.5% | 31.5 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c <7.0% | 50 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms | HbA1c ≤6.5% | 26.3 percentage of participants |
p-value: 0.273Fisher Exact
p-value: 0.287Fisher Exact
p-value: 0.879Fisher Exact
p-value: 0.722Fisher Exact
Secondary
Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment
HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole/Liter (mmol/L) (≤70 milligram/deciliter \[mg/dL\]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).
Time frame: Week 12
Population: All randomized participants who took at least one dose of study drug, last observation carried forward (LOCF). Arms are combined due to
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment | HbA1c <7.0% | 11.96 percentage of participants |
| Insulin Glargine | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment | HbA1c ≤6.5% | 6.52 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment | HbA1c <7.0% | 16.49 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment | HbA1c ≤6.5% | 7.98 percentage of participants |
p-value: 0.375Fisher Exact
p-value: 0.811Fisher Exact
Secondary
Percentage of Participants With Hypoglycemia From Baseline Through Week 12
Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).
Time frame: Baseline through Week 12
Population: All randomized participants who took at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants With Hypoglycemia From Baseline Through Week 12 | 63.4 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With Hypoglycemia From Baseline Through Week 12 | 54.0 percentage of participants |
p-value: 0.162Fisher Exact
Secondary
Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).
Time frame: Baseline through Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | 63.4 percentage of participants |
| LY2605541 Algorithm 1 | Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | 47.5 percentage of participants |
| LY2605541 Algorithm 2 | Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | 54.2 percentage of participants |
p-value: 0.046Fisher Exact
p-value: 0.224Fisher Exact
Secondary
Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 12 Endpoint
The drug (LY2605541) concentration at steady state (Css) is calculated from the clearance (Liter/hour) and the final dose of the participants. Clearance was estimated using population-based approaches.
Time frame: Week 12
Population: Participants who took at least one dose of study drug and had measurements at Week 12.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 12 Endpoint | 4258 picomoles per liter (pMol/L) | Geometric Coefficient of Variation 70.8 |
Secondary
Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12
Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30.
Time frame: Baseline through Week 12
Population: All randomized participants who took at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 | 1.52 Number of Hypoglycemia episodes/30 days | Standard Deviation 2.08 |
| LY2605541 Algorithm 1 | Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 | 1.34 Number of Hypoglycemia episodes/30 days | Standard Deviation 2.47 |
p-value: 0.804Negative Binomial Model
Secondary
Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30.
Time frame: Baseline through Week 12
Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | 1.52 Number of Hypoglycemia episodes/30 days | Standard Deviation 2.08 |
| LY2605541 Algorithm 1 | Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | 1.25 Number of Hypoglycemia episodes/30 days | Standard Deviation 2.27 |
| LY2605541 Algorithm 2 | Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms | 1.27 Number of Hypoglycemia episodes/30 days | Standard Deviation 2.2 |
p-value: 0.561Negative Binomial Model
p-value: 0.518Negative Binomial Model