| Primary | Change From Baseline to 24 Weeks in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline of response, treatment (LY2963016, LANTUS), pooled country, basal insulin at entry (yes/no), sulfonylurea (SU) use (yes/no), visit, treatment and visit*treatment in the model. | All randomized participants who received at least 1 dose of study drug and with a Baseline and at least 1 post-Baseline HbA1c measure. | Posted | | Least Squares Mean | Standard Error | Percentage of glycosylated hemoglobin | | Baseline, 24 weeks | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
| | | Title | Denominators | Categories |
|---|
| | | Title | Measurements |
|---|
| - OG000-1.25± 0.066
- OG001-1.22± 0.067
|
|
| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | Mixed Models Analysis | | 0.693 | | Mean Difference (Final Values) | -0.04 | | | 2-Sided | 95 | -0.22 | 0.15 | | | | | Non-Inferiority or Equivalence | The primary treatment comparison was to compare LY2963016 versus Lantus at the non-inferiority margin of +0.4%. If the upper limit of the 95% confidence interval on the change from baseline to 24-week HbA1c level for LY2963016 versus Lantus was below +0.4%, then LY2963016 would be declared non-inferior to Lantus. | |
|
| Secondary | Percentage of Participants With HbA1c <7% and ≤6.5% | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. | All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline HbA1c measure; last observation carried forward (LOCF). | Posted | | Number | | Percentage of participants | | Endpoint [up to 24 weeks] | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values | Seven-point SMBG are completed at the following timepoints: Before Morning Meal, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, Bed Time and 03:00 AM hours. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline HbA1c, country, sulfonylurea use, basal insulin status at study entry, visit, treatment and visit*treatment in the model. | All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline SMBG measure. | Posted | | Least Squares Mean | Standard Error | Millimoles per liter (mmol/L) | | Baseline, Week 24 | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Intra-Participant Variability in Fasting Blood Glucose (FBG) | Fasting blood glucose (FBG) is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Intra-Participant FBG variability was calculated based on the standard deviation (SD) of the morning pre-meal BG value. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline HbA1c, country, sulfonylurea use, basal insulin status at study entry, visit, treatment and visit*treatment in the model. | All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline fasting blood glucose measure. | Posted | | Least Squares Mean | Standard Error | mmol/L | | Week 24 | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Basal Insulin Dose Units Per Day | Units of Basal Insulin dose taken per day (U/day). Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, baseline HbA1c, country, sulfonylurea use, basal insulin status at study entry, visit, treatment and visit*treatment in the model. | All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline Basal Insulin Dose. | Posted | | Least Squares Mean | Standard Error | Units per day (U/day) | | Week 24 | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Basal Insulin Dose Per Body Weight (U/kg/Day) | Basal Insulin dose in units (U) per body weight in kilograms (kg) per day. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, baseline HbA1c, country, sulfonylurea use, basal insulin status at study entry, visit, treatment and visit*treatment in the model. | All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline Basal Insulin Dose per Body Weight measure. | Posted | | Least Squares Mean | Standard Error | units per kilogram per day (U/kg/day) | | Week 24 | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Change From Baseline to 24 Weeks in Body Weight | Change from baseline in body weight. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, baseline HbA1c, country, sulfonylurea use, basal insulin status at study entry, visit, treatment and visit*treatment in the model. | All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline body weight measure. | Posted | | Least Squares Mean | Standard Error | Kilogram (kg) | | Baseline, 24 Weeks | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Insulin Treatment Satisfaction Questionnaire (ITSQ) Score | ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items divided into 5 domains of satisfaction: Inconvenience of Regimen [(IR) 5 items: domain scores range (DSR) 5-35], Lifestyle Flexibility [(LF) 3 items: DSR 3-21], Glycemic Control [(GC) 3 items: DSR 3-21], Hypoglycemic Control [(HC) 5 items: DSR 5-35], Insulin Delivery Device [(IDD) 6 items: DSR 6-42]. All items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. ITSQ Total Overall Raw Scores range from 22-154. Both raw domain and overall scores are transformed on a scale of 0-100, where transformed score=100*[(7-mean raw score)/6]. Higher scores indicate better treatment satisfaction. LS means was determined by MMRM with baseline of response, baseline HbA1c, country, sulfonylurea use, basal insulin status at study entry, visit, treatment and visit*treatment in the model. | All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline ITSQ measure. | Posted | | Least Squares Mean | Standard Error | units on a scale | | Week 4 and Week 24 | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Percentage of Participants With Detectable Anti-Drug Antibodies to LY2963016 or LANTUS® | The percentage of participants with detected insulin antibodies were summarized as counts and percentages at baseline, at each visit, at the 24-week endpoint (LOCF), and overall for the 24-week treatment period. | All randomized participants who received at least 1 dose of study drug and with a Baseline and at least 1 post-Baseline with detectable anti-drug antibodies; last observation carried forward (LOCF). | Posted | | Number | | Percentage of participants | | Endpoint [up to 24 weeks] | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). | | OG001 | LANTUS® | Insulin naive participants started on 10 U LANTUS® given SC QD for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or NPH QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Rate of Hypoglycemic Events Adjusted Per 1 Year | The rate of hypoglycemic events were analyzed at baseline, titration, maintenance, and overall study periods and at endpoint using the Wilcoxon test. In addition, a negative binomial model was used as a sensitivity analysis. A hypoglycemic event is defined as any time a participant has a blood glucose (BG) level of ≤70 milligrams per deciliter (mg/dL) even if the event was not associated with signs, symptoms, or treatment consistent with current guidelines (American Diabetes Association 2005). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrates, glucagons, or other resuscitative actions. Severe Hypoglycemic events may or may not have a reported BG ≤70 mg/dL. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. | All randomized participants who received at 1 dose of study drug with Baseline at least 1 post-Baseline hypoglycemic event; last observation carried forward (LOCF). | Posted | | Mean | Standard Deviation | Hypoglycemic events per 1 year | | Baseline through Endpoint [up to 24 weeks] | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|
| Secondary | Percentage of Participants With Hypoglycemic Events | The percentage of participants (with at least 1 hypoglycemic event (total, severe, nocturnal, and others) or incidence during the study was analyzed using Fisher's exact test. A hypoglycemic event is defined as any time a participant has a blood glucose (BG) level of ≤70 milligrams per deciliter (mg/dL) even if the event was not associated with signs, symptoms, or treatment consistent with current guidelines (American Diabetes Association 2005). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrates, glucagons, or other resuscitative actions. Severe Hypoglycemic events may or may not have a reported BG ≤70 mg/dL. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. | All randomized participants who had a post-baseline measurement for Hypoglycemic Events; last observation carried forward (LOCF). | Posted | | Number | | Percentage of participants | | Endpoint [up to 24 weeks] | | | | ID | Title | Description |
|---|
| OG000 | LY2963016 | Insulin naive participants started on 10 units (U) LY2963016 given subcutaneously (SC) once a day (QD) for 24 weeks. Participants entering the study on LANTUS®, insulin detemir or neutral protamine Hagedorn (NPH) QD were started at the same dose SC. Participants entering on insulin detemir or NPH twice a day (BID) were started at 80% of the total daily dose SC. Participants-driven titration was followed to include the addition of 1 U/day until the fasting blood glucose (FBG) level reaches ≤100 mg/dL (5.6 mmol/L). Participants were allowed to continue oral antihyperglycemic medication (OAM). |
|