Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to determine if LY2189265 is effective in reducing hemoglobin A1c (HbA1c) and safe, as compared to Insulin Glargine in participants with Type 2 Diabetes. Participants must also be taking metformin and glimepiride.
Detailed description
Rescue therapy refers to 1 of 2 types of additional therapy, each given for a different reason: any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who received rescue therapy were included in the analysis population, but only measurements obtained prior to the beginning of rescue therapy were included in specified efficacy analyses.
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
* Type 2 Diabetes not well controlled on 1, 2, or 3 oral antidiabetic medications (at least one of them must be metformin and/or a sulfonylurea) 1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication 2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications * Accept treatment with metformin and glimepiride throughout the study, as per protocol * Willing to inject subcutaneous medication once weekly for LY2189265 or once daily for Insulin Glargine. * Stable weight for 3 months prior to screening * Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m\^2) * Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug
Exclusion criteria
* Type 1 Diabetes * HbA1c equal to or less than 6.5 at randomization * Chronic insulin use * Taking drugs to promote weight loss by prescription or over the counter * Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled * History of Heart Failure New York Heart Classification III or IV, or acute myocardial infarction, or stroke within 2 months of screening * Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility * Hepatitis or liver disease or ALT (alanine transaminase) greater than 3.0 of upper normal limit * Acute or chronic pancreatitis of any form * Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatinine clearance of less than 60 milliliters per minute (ml/min) * History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer * A serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/ml) at screening * Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis * History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years * Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing * Organ transplant except cornea * Have enrolled in another clinical trial within the last 30 days * Have previously signed an informed consent or participated in a LY2189265 study * Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 52 weeks | Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 26, 52, and 78 weeks | Number of participants achieving HbA1c levels less than 7.0% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model. |
| Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 26, 52, and 78 weeks | Number of participants achieving HbA1c levels less than or equal to 6.5% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model. |
| Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | Baseline, 26, 52, and 78 weeks | The self-monitored blood glucose (SMBG) data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 3 AM or 5 hours after bedtime. Least Squares (LS) means of the mean of the 8 time points (Daily Mean) were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | Baseline, 52, and 78 weeks | The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S), as percentages of a normal reference population (normal young adults). The normal reference population for both HOMA2-B and HOMA-2S were set at 100%. Least Squares (LS) means of change from baseline of C-peptide based HOMA2-%B and HOMA2-%S were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 and 78 Weeks in Glucagon Concentration | Baseline, 52, and 78 weeks | Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52 and 78 Weeks for Body Weight | Baseline, 26, 52, and 78 weeks | Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | Baseline, 26, 52, and 78 weeks | Body mass index (BMI) is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | Baseline, 26, 52, and 78 weeks | The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a 100-mm visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline. |
| Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | Baseline, 26, 52, and 78 weeks | The Impact of Weight on Activities of Daily Living questionnaire (renamed the Ability to Perform Physical Activities of Daily Living Questionnaire \[APPADL\]) contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | Baseline, 26, 52, and 78 weeks | The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | Baseline, 26, 52, and 78 weeks | The Low Blood Sugar Survey (LBSS) contains 33 items comprised of 2 subscales (behavior and worry), each of which is rated on a 5-point numeric rating scale from 0 (never) to 4 (almost always). It captures behavioral changes associated with the concerns and experiences of hypoglycemia and the degree to which participants are worried about certain aspects associated with hypoglycemia during the previous 4 weeks. The behavior (or avoidance) subscale has 15 items, and the worry (or affect) subscale has 18 items. Subscale scores are calculated by summing participant responses to items (behavior range 0-60; worry range 0-72). A total score is calculated as the sum of both subscales (range 0-132). Higher scores indicate greater negative impact on subscales and total score. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 26, 52, and 78 weeks | A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 26 weeks, and 78 weeks | Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate. |
| Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Baseline through 26, 52, and 78 weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 26, 52, and 78 weeks | Additional intervention was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. The number of participants requiring additional intervention due to hyperglycemia is summarized cumulatively at 26, 52, and 78 weeks. |
| Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Baseline, 26, 52, and 78 weeks | Amylase (total and pancreas-derived) and lipase concentrations were measured. |
| Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | Baseline through 26, 52, and 78 weeks | The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | Baseline, 26, 52, and 78 weeks | — |
| Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Baseline through 26, 52, and 78 weeks | Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with adjudicated CV events is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | Baseline, 26, 52, and 78 weeks | Sitting pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | Baseline, 26, 52, and 78 weeks | Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | Baseline, 26, 52, and 78 weeks | Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | Baseline, 26, 52, and 78 weeks | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) | Baseline, 26, 52, 78, and 83 weeks | LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed at baseline, 26, 52, and 78 weeks, and at the safety follow-up visit 30 days after study drug discontinuation (83 weeks). The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA at each time point were summarized. |
| Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Baseline through 26, 52, and 78 weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Croatia, Czechia, France, Greece, Hungary, India, Italy, Mexico, Poland, Romania, Slovakia, South Korea, Spain, Sweden, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2189265 1.5 mg LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks | 273 |
| LY2189265 0.75 mg LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks | 272 |
| Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks
Metformin: at least 1500 milligram per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks | 262 |
| Total | 807 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 8 | 5 |
| Overall Study | Death | 0 | 1 | 2 |
| Overall Study | Entry Criteria Not Met | 3 | 2 | 0 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 3 | 3 |
| Overall Study | Physician Decision | 3 | 3 | 3 |
| Overall Study | Protocol Violation | 0 | 2 | 1 |
| Overall Study | Treatment Non-compliance | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 11 | 7 | 11 |
Baseline characteristics
| Characteristic | Total | LY2189265 1.5 mg | LY2189265 0.75 mg | Insulin Glargine |
|---|---|---|---|---|
| Age, Continuous | 56.66 years STANDARD_DEVIATION 9.47 | 56.24 years STANDARD_DEVIATION 9.76 | 56.56 years STANDARD_DEVIATION 9.27 | 57.21 years STANDARD_DEVIATION 9.38 |
| Body Mass Index (BMI) | 31.55 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.46 | 31.23 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.21 | 31.51 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.41 | 31.91 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.76 |
| Body Weight | 86.31 kilograms STANDARD_DEVIATION 18.56 | 85.13 kilograms STANDARD_DEVIATION 17.9 | 86.18 kilograms STANDARD_DEVIATION 18.15 | 87.66 kilograms STANDARD_DEVIATION 19.62 |
| Duration of Diabetes | 9.10 years STANDARD_DEVIATION 6.04 | 9.13 years STANDARD_DEVIATION 6.22 | 9.28 years STANDARD_DEVIATION 5.93 | 8.87 years STANDARD_DEVIATION 5.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 291 Participants | 98 Participants | 96 Participants | 97 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 516 Participants | 175 Participants | 176 Participants | 165 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Fasting Serum Glucose | 9.07 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.69 | 9.16 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.73 | 8.96 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.7 | 9.08 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.66 |
| Glycosylated Hemoglobin (HbA1c) | 8.14 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.99 | 8.18 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.03 | 8.13 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.98 | 8.10 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.95 |
| Race (NIH/OMB) American Indian or Alaska Native | 89 Participants | 29 Participants | 31 Participants | 29 Participants |
| Race (NIH/OMB) Asian | 137 Participants | 48 Participants | 46 Participants | 43 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 570 Participants | 193 Participants | 193 Participants | 184 Participants |
| Region of Enrollment Argentina | 163 participants | 55 participants | 54 participants | 54 participants |
| Region of Enrollment Australia | 39 participants | 13 participants | 13 participants | 13 participants |
| Region of Enrollment Belgium | 15 participants | 7 participants | 5 participants | 3 participants |
| Region of Enrollment Brazil | 18 participants | 6 participants | 5 participants | 7 participants |
| Region of Enrollment Canada | 75 participants | 26 participants | 25 participants | 24 participants |
| Region of Enrollment Croatia | 11 participants | 3 participants | 4 participants | 4 participants |
| Region of Enrollment Czech Republic | 39 participants | 12 participants | 14 participants | 13 participants |
| Region of Enrollment France | 6 participants | 2 participants | 3 participants | 1 participants |
| Region of Enrollment Greece | 19 participants | 6 participants | 6 participants | 7 participants |
| Region of Enrollment Hungary | 47 participants | 16 participants | 16 participants | 15 participants |
| Region of Enrollment India | 84 participants | 30 participants | 27 participants | 27 participants |
| Region of Enrollment Italy | 6 participants | 2 participants | 3 participants | 1 participants |
| Region of Enrollment Korea, Republic of | 5 participants | 1 participants | 3 participants | 1 participants |
| Region of Enrollment Mexico | 84 participants | 29 participants | 28 participants | 27 participants |
| Region of Enrollment Poland | 51 participants | 16 participants | 18 participants | 17 participants |
| Region of Enrollment Romania | 67 participants | 23 participants | 22 participants | 22 participants |
| Region of Enrollment Slovakia | 2 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Spain | 35 participants | 10 participants | 12 participants | 13 participants |
| Region of Enrollment Sweden | 3 participants | 2 participants | 0 participants | 1 participants |
| Region of Enrollment Taiwan | 38 participants | 13 participants | 13 participants | 12 participants |
| Sex: Female, Male Female | 393 Participants | 129 Participants | 136 Participants | 128 Participants |
| Sex: Female, Male Male | 414 Participants | 144 Participants | 136 Participants | 134 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 | 199 / 273 | 190 / 272 | 187 / 262 |
| serious Total, serious adverse events | 32 / 273 | 28 / 272 | 33 / 262 |
Outcome results
Primary
Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.08 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| LY2189265 0.75 mg | Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.76 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| Insulin Glargine | Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.63 percentage of glycosylated hemoglobin | Standard Error 0.06 |
Comparison: The study was designed with 90% power to detect non-inferiority of LY2189265 1.5 mg vs insulin glargine on HbA1c change from baseline at the 52-week primary endpoint with a margin of 0.4%, a standard deviation of 1.3%, and a 1-sided alpha of 0.025 assuming no true difference between treatments. This corresponds to 223 participants per arm, with an assumed drop-out rate of 20%.p-value: <0.00195% CI: [-0.6, -0.29]ANCOVA
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.29, 0.02]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.6, -0.29]ANCOVA
Comparison: Superiority analysis.p-value: 0.0595% CI: [-0.29, 0.02]ANCOVA
Secondary
Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index
Body mass index (BMI) is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable BMI data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 52 weeks (n=250, 252, 238) | -0.64 kilograms per square meter (kg/m^2) | Standard Error 0.08 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 26 weeks (n=257, 261, 245) | -0.64 kilograms per square meter (kg/m^2) | Standard Error 0.07 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 78 weeks (n=246, 244, 238) | -0.64 kilograms per square meter (kg/m^2) | Standard Error 0.09 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 52 weeks (n=250, 252, 238) | -0.39 kilograms per square meter (kg/m^2) | Standard Error 0.08 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 26 weeks (n=257, 261, 245) | -0.50 kilograms per square meter (kg/m^2) | Standard Error 0.07 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 78 weeks (n=246, 244, 238) | -0.39 kilograms per square meter (kg/m^2) | Standard Error 0.09 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 26 weeks (n=257, 261, 245) | 0.44 kilograms per square meter (kg/m^2) | Standard Error 0.07 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 78 weeks (n=246, 244, 238) | 0.59 kilograms per square meter (kg/m^2) | Standard Error 0.1 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index | 52 weeks (n=250, 252, 238) | 0.62 kilograms per square meter (kg/m^2) | Standard Error 0.08 |
Secondary
Change From Baseline to 26, 52 and 78 Weeks for Body Weight
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable body weight data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 52 weeks | -1.87 kilogram (kg) | Standard Error 0.24 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 26 weeks | -1.82 kilogram (kg) | Standard Error 0.2 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 78 weeks | -1.96 kilogram (kg) | Standard Error 0.26 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 52 weeks | -1.33 kilogram (kg) | Standard Error 0.24 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 26 weeks | -1.47 kilogram (kg) | Standard Error 0.2 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 78 weeks | -1.54 kilogram (kg) | Standard Error 0.26 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 26 weeks | 1.01 kilogram (kg) | Standard Error 0.2 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 78 weeks | 1.28 kilogram (kg) | Standard Error 0.26 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Body Weight | 52 weeks | 1.44 kilogram (kg) | Standard Error 0.24 |
p-value: <0.00195% CI: [2.33, 3.33]ANCOVA
p-value: <0.00195% CI: [1.99, 2.99]ANCOVA
p-value: <0.00195% CI: [2.71, 3.9]ANCOVA
p-value: <0.00195% CI: [2.17, 3.36]ANCOVA
p-value: <0.00195% CI: [2.59, 3.89]ANCOVA
p-value: <0.00195% CI: [2.17, 3.46]ANCOVA
Secondary
Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles
The self-monitored blood glucose (SMBG) data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; bedtime; and 3 AM or 5 hours after bedtime. Least Squares (LS) means of the mean of the 8 time points (Daily Mean) were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable SMBG data. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 78 weeks (n=172, 164, 168) | -1.55 millimoles per liter (mmol/L) | Standard Error 0.13 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 52 weeks (n=180, 185, 176) | -1.69 millimoles per liter (mmol/L) | Standard Error 0.11 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 26 weeks (n=199, 204, 190) | -1.79 millimoles per liter (mmol/L) | Standard Error 0.1 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 78 weeks (n=172, 164, 168) | -1.15 millimoles per liter (mmol/L) | Standard Error 0.12 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 52 weeks (n=180, 185, 176) | -1.32 millimoles per liter (mmol/L) | Standard Error 0.11 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 26 weeks (n=199, 204, 190) | -1.46 millimoles per liter (mmol/L) | Standard Error 0.1 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 52 weeks (n=180, 185, 176) | -1.44 millimoles per liter (mmol/L) | Standard Error 0.11 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 26 weeks (n=199, 204, 190) | -1.58 millimoles per liter (mmol/L) | Standard Error 0.1 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 78 weeks (n=172, 164, 168) | -1.47 millimoles per liter (mmol/L) | Standard Error 0.13 |
p-value: 0.109Mixed Models Analysis
p-value: 0.335Mixed Models Analysis
p-value: 0.091Mixed Models Analysis
p-value: 0.4Mixed Models Analysis
p-value: 0.641Mixed Models Analysis
p-value: 0.055Mixed Models Analysis
Secondary
Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension
The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a 100-mm visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable EQ-5D data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 26 weeks (n=257, 254, 249) | 0.01 units on a scale | Standard Error 0.01 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 52 weeks (n=259, 260, 253) | 0.01 units on a scale | Standard Error 0.01 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 78 weeks (n=259, 260, 253) | 0.01 units on a scale | Standard Error 0.01 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 26 weeks (n=253, 252, 243) | 3.3 units on a scale | Standard Error 0.83 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 52 weeks (n=260, 258, 252) | 3.2 units on a scale | Standard Error 0.85 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 78 weeks (n=260, 258, 252) | 3.8 units on a scale | Standard Error 0.85 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 78 weeks (n=260, 258, 252) | 3.2 units on a scale | Standard Error 0.85 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 78 weeks (n=259, 260, 253) | 0.00 units on a scale | Standard Error 0.01 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 26 weeks (n=253, 252, 243) | 3.4 units on a scale | Standard Error 0.84 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 52 weeks (n=260, 258, 252) | 2.3 units on a scale | Standard Error 0.85 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 26 weeks (n=257, 254, 249) | 0.00 units on a scale | Standard Error 0.01 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 52 weeks (n=259, 260, 253) | 0.00 units on a scale | Standard Error 0.01 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 52 weeks (n=260, 258, 252) | 1.1 units on a scale | Standard Error 0.88 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 52 weeks (n=259, 260, 253) | -0.04 units on a scale | Standard Error 0.01 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 78 weeks (n=259, 260, 253) | 0.00 units on a scale | Standard Error 0.01 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 78 weeks (n=260, 258, 252) | 2.2 units on a scale | Standard Error 0.89 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | EQ-5D UK, 26 weeks (n=257, 254, 249) | -0.01 units on a scale | Standard Error 0.01 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension | VAS, 26 weeks (n=253, 252, 243) | 0.8 units on a scale | Standard Error 0.86 |
Secondary
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living
The Impact of Weight on Activities of Daily Living questionnaire (renamed the Ability to Perform Physical Activities of Daily Living Questionnaire \[APPADL\]) contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable APPADL data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 52 weeks (n=260, 261, 249) | 0.9 units on a scale | Standard Error 0.31 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 26 weeks (n=256, 256, 248) | 0.7 units on a scale | Standard Error 0.3 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 78 weeks (n=260, 261, 249) | 1.0 units on a scale | Standard Error 0.31 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 52 weeks (n=260, 261, 249) | 0.4 units on a scale | Standard Error 0.31 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 26 weeks (n=256, 256, 248) | 0.1 units on a scale | Standard Error 0.3 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 78 weeks (n=260, 261, 249) | 0.3 units on a scale | Standard Error 0.31 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 26 weeks (n=256, 256, 248) | -0.3 units on a scale | Standard Error 0.3 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 78 weeks (n=260, 261, 249) | -0.3 units on a scale | Standard Error 0.32 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living | 52 weeks (n=260, 261, 249) | -0.6 units on a scale | Standard Error 0.32 |
Secondary
Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception
The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable IW-SP data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 78 weeks (n=260, 261, 252) | 0.5 units on a scale | Standard Error 0.16 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 52 weeks (n=260, 261, 252) | 0.5 units on a scale | Standard Error 0.16 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 26 weeks (n=258, 258, 251) | 0.1 units on a scale | Standard Error 0.16 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 52 weeks (n=260, 261, 252) | 0.2 units on a scale | Standard Error 0.16 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 26 weeks (n=258, 258, 251) | 0.2 units on a scale | Standard Error 0.16 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 78 weeks (n=260, 261, 252) | 0.3 units on a scale | Standard Error 0.15 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 26 weeks (n=258, 258, 251) | -0.1 units on a scale | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 78 weeks (n=260, 261, 252) | 0.1 units on a scale | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception | 52 weeks (n=260, 261, 252) | 0.1 units on a scale | Standard Error 0.16 |
Secondary
Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey
The Low Blood Sugar Survey (LBSS) contains 33 items comprised of 2 subscales (behavior and worry), each of which is rated on a 5-point numeric rating scale from 0 (never) to 4 (almost always). It captures behavioral changes associated with the concerns and experiences of hypoglycemia and the degree to which participants are worried about certain aspects associated with hypoglycemia during the previous 4 weeks. The behavior (or avoidance) subscale has 15 items, and the worry (or affect) subscale has 18 items. Subscale scores are calculated by summing participant responses to items (behavior range 0-60; worry range 0-72). A total score is calculated as the sum of both subscales (range 0-132). Higher scores indicate greater negative impact on subscales and total score. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable LBSS data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 78 weeks (n=258, 259, 245) | -4.6 units on a scale | Standard Error 0.82 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 52 weeks (n=258, 259, 245) | -4.2 units on a scale | Standard Error 0.83 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 26 weeks (n=255, 255, 244) | -2.8 units on a scale | Standard Error 0.95 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 26 weeks (n=255, 255, 244) | -2.4 units on a scale | Standard Error 0.96 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 78 weeks (n=258, 259, 245) | -4.7 units on a scale | Standard Error 0.82 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 52 weeks (n=258, 259, 245) | -4.1 units on a scale | Standard Error 0.83 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 52 weeks (n=258, 259, 245) | -1.0 units on a scale | Standard Error 0.86 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 26 weeks (n=255, 255, 244) | 0.3 units on a scale | Standard Error 0.98 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey | 78 weeks (n=258, 259, 245) | -2.0 units on a scale | Standard Error 0.85 |
Secondary
Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure
Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable blood pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 52 weeks (n=250, 252, 240) | -0.26 milliliter of mercury (mmHG) | Standard Error 0.48 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 78 weeks (n=246, 244, 238) | -0.70 milliliter of mercury (mmHG) | Standard Error 0.85 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 78 weeks (n=246, 244, 238) | -0.44 milliliter of mercury (mmHG) | Standard Error 0.52 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 26 weeks (n=257, 261, 245) | -1.28 milliliter of mercury (mmHG) | Standard Error 0.78 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 26 weeks (n=257, 261, 245) | -0.16 milliliter of mercury (mmHG) | Standard Error 0.49 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 52 weeks (n=250, 252, 240) | 0.17 milliliter of mercury (mmHG) | Standard Error 0.81 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 26 weeks (n=257, 261, 245) | -0.17 milliliter of mercury (mmHG) | Standard Error 0.48 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 52 weeks (n=250, 252, 240) | -0.19 milliliter of mercury (mmHG) | Standard Error 0.47 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 78 weeks (n=246, 244, 238) | -0.36 milliliter of mercury (mmHG) | Standard Error 0.52 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 52 weeks (n=250, 252, 240) | 0.09 milliliter of mercury (mmHG) | Standard Error 0.8 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 26 weeks (n=257, 261, 245) | -1.60 milliliter of mercury (mmHG) | Standard Error 0.78 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 78 weeks (n=246, 244, 238) | -0.59 milliliter of mercury (mmHG) | Standard Error 0.85 |
| Insulin Glargine | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 78 weeks (n=246, 244, 238) | -1.04 milliliter of mercury (mmHG) | Standard Error 0.53 |
| Insulin Glargine | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 26 weeks (n=257, 261, 245) | -0.03 milliliter of mercury (mmHG) | Standard Error 0.8 |
| Insulin Glargine | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 52 weeks (n=250, 252, 240) | 0.51 milliliter of mercury (mmHG) | Standard Error 0.83 |
| Insulin Glargine | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | SBP, 78 weeks (n=246, 244, 238) | 0.51 milliliter of mercury (mmHG) | Standard Error 0.87 |
| Insulin Glargine | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 26 weeks (n=257, 261, 245) | -0.29 milliliter of mercury (mmHG) | Standard Error 0.5 |
| Insulin Glargine | Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure | DBP, 52 weeks (n=250, 252, 240) | -0.93 milliliter of mercury (mmHG) | Standard Error 0.49 |
Secondary
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable ECG QTcF or PR Interval data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=240, 245, 229) | -1.71 milliseconds (msec) | Standard Error 0.939 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n=231, 240, 228) | 1.55 milliseconds (msec) | Standard Error 1.074 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 78 weeks (n=221, 220, 222) | 1.66 milliseconds (msec) | Standard Error 1.045 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=240, 245, 229) | 2.78 milliseconds (msec) | Standard Error 0.849 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=230, 240, 227) | 2.61 milliseconds (msec) | Standard Error 0.853 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 78 weeks (n=221, 220, 222) | 2.62 milliseconds (msec) | Standard Error 1.034 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 78 weeks (n=221, 220, 222) | 3.27 milliseconds (msec) | Standard Error 1.026 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=240, 245, 229) | -0.10 milliseconds (msec) | Standard Error 0.926 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=240, 245, 229) | 2.33 milliseconds (msec) | Standard Error 0.836 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=230, 240, 227) | 1.88 milliseconds (msec) | Standard Error 0.835 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n=231, 240, 228) | 1.34 milliseconds (msec) | Standard Error 1.054 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 78 weeks (n=221, 220, 222) | 3.44 milliseconds (msec) | Standard Error 1.039 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n=231, 240, 228) | 3.70 milliseconds (msec) | Standard Error 1.088 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 78 weeks (n=221, 220, 222) | 4.44 milliseconds (msec) | Standard Error 1.053 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 78 weeks (n=221, 220, 222) | 1.21 milliseconds (msec) | Standard Error 1.043 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=240, 245, 229) | 1.24 milliseconds (msec) | Standard Error 0.873 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=240, 245, 229) | 1.24 milliseconds (msec) | Standard Error 0.962 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=230, 240, 227) | 1.50 milliseconds (msec) | Standard Error 0.868 |
Secondary
Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate
Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable ECG heart rate data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 52 weeks (n=232, 242, 231) | 2.41 beats per minute (bpm) | Standard Error 0.564 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 26 weeks (n=241, 247, 231) | 2.64 beats per minute (bpm) | Standard Error 0.539 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 78 weeks (n=223, 222, 225) | 2.49 beats per minute (bpm) | Standard Error 0.592 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 52 weeks (n=232, 242, 231) | 0.38 beats per minute (bpm) | Standard Error 0.551 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 26 weeks (n=241, 247, 231) | 0.90 beats per minute (bpm) | Standard Error 0.529 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 78 weeks (n=223, 222, 225) | 0.47 beats per minute (bpm) | Standard Error 0.588 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 26 weeks (n=241, 247, 231) | -1.24 beats per minute (bpm) | Standard Error 0.549 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 78 weeks (n=223, 222, 225) | -0.26 beats per minute (bpm) | Standard Error 0.594 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate | 52 weeks (n=232, 242, 231) | -1.01 beats per minute (bpm) | Standard Error 0.568 |
Secondary
Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes
Amylase (total and pancreas-derived) and lipase concentrations were measured.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable pancreatic enzyme data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 52 weeks | 4.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 26 weeks | 4.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 52 weeks | 4.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 78 weeks | 4.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 26 weeks | 3.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 52 weeks | 3.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 78 weeks | 2.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 26 weeks | 5.000 units/liter |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 78 weeks | 4.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 52 weeks | 3.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 78 weeks | 4.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 26 weeks | 4.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 52 weeks | 4.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 26 weeks | 5.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 52 weeks | 5.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 26 weeks | 3.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 78 weeks | 2.000 units/liter |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 78 weeks | 4.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 78 weeks | 0.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 26 weeks | 1.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 52 weeks | -1.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (pancreas-derived), 52 weeks | 1.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 78 weeks | -2.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 78 weeks | 1.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 26 weeks | 2.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Amylase (total), 52 weeks | 3.000 units/liter |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes | Lipase, 26 weeks | -1.000 units/liter |
Secondary
Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable serum calcitonin data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 52 weeks (n=266, 269, 259) | 0.128 picogram/milliliter | Standard Deviation 1.2 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 26 weeks (n=266, 267, 258) | 0.163 picogram/milliliter | Standard Deviation 1.31 |
| LY2189265 1.5 mg | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 78 weeks (n=267, 269, 259) | 0.086 picogram/milliliter | Standard Deviation 1.31 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 52 weeks (n=266, 269, 259) | 0.132 picogram/milliliter | Standard Deviation 1.32 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 26 weeks (n=266, 267, 258) | 0.097 picogram/milliliter | Standard Deviation 1.2 |
| LY2189265 0.75 mg | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 78 weeks (n=267, 269, 259) | 0.035 picogram/milliliter | Standard Deviation 1.2 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 26 weeks (n=266, 267, 258) | 0.149 picogram/milliliter | Standard Deviation 1.3 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 78 weeks (n=267, 269, 259) | 0.151 picogram/milliliter | Standard Deviation 1.73 |
| Insulin Glargine | Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin | 52 weeks (n=266, 269, 259) | 0.176 picogram/milliliter | Standard Deviation 1.62 |
Secondary
Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, 26 weeks, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | 26 weeks (n=263, 266, 258) | -1.16 percent | Standard Error 0.06 |
| LY2189265 1.5 mg | Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | 78 weeks (n=263, 267, 259) | -0.90 percent | Standard Error 0.07 |
| LY2189265 0.75 mg | Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | 26 weeks (n=263, 266, 258) | -0.89 percent | Standard Error 0.05 |
| LY2189265 0.75 mg | Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | 78 weeks (n=263, 267, 259) | -0.62 percent | Standard Error 0.07 |
| Insulin Glargine | Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | 26 weeks (n=263, 266, 258) | -0.65 percent | Standard Error 0.06 |
| Insulin Glargine | Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | 78 weeks (n=263, 267, 259) | -0.59 percent | Standard Error 0.07 |
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.38, -0.1]ANCOVA
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.65, -0.37]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.65, -0.37]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.38, -0.1]ANCOVA
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.5, -0.13]ANCOVA
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.21, 0.15]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.5, -0.13]ANCOVA
Comparison: Superiority analysis.p-value: 0.37895% CI: [-0.21, 0.15]ANCOVA
Secondary
Change From Baseline to 52 and 78 Weeks in Glucagon Concentration
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable glucagon data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 52 and 78 Weeks in Glucagon Concentration | 52 weeks (n=232, 231, 228) | -3.91 picomoles per liter (pmol/L) | Standard Error 0.47 |
| LY2189265 1.5 mg | Change From Baseline to 52 and 78 Weeks in Glucagon Concentration | 78 weeks (n=235, 235, 232) | -3.57 picomoles per liter (pmol/L) | Standard Error 0.47 |
| LY2189265 0.75 mg | Change From Baseline to 52 and 78 Weeks in Glucagon Concentration | 52 weeks (n=232, 231, 228) | -3.31 picomoles per liter (pmol/L) | Standard Error 0.47 |
| LY2189265 0.75 mg | Change From Baseline to 52 and 78 Weeks in Glucagon Concentration | 78 weeks (n=235, 235, 232) | -3.37 picomoles per liter (pmol/L) | Standard Error 0.47 |
| Insulin Glargine | Change From Baseline to 52 and 78 Weeks in Glucagon Concentration | 52 weeks (n=232, 231, 228) | -3.85 picomoles per liter (pmol/L) | Standard Error 0.47 |
| Insulin Glargine | Change From Baseline to 52 and 78 Weeks in Glucagon Concentration | 78 weeks (n=235, 235, 232) | -3.65 picomoles per liter (pmol/L) | Standard Error 0.47 |
Secondary
Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S)
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S), as percentages of a normal reference population (normal young adults). The normal reference population for both HOMA2-B and HOMA-2S were set at 100%. Least Squares (LS) means of change from baseline of C-peptide based HOMA2-%B and HOMA2-%S were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 with evaluable HOMA2-%B or HOMA2-%S data. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B, 78 weeks (n=167, 165) | 28.54 percentage of HOMA2 | Standard Error 4.78 |
| LY2189265 1.5 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S, 78 weeks (n=167, 165) | -2.64 percentage of HOMA2 | Standard Error 1.23 |
| LY2189265 1.5 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S, 52 weeks (n=175,181) | -2.89 percentage of HOMA2 | Standard Error 1.21 |
| LY2189265 1.5 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B, 52 weeks (n=175, 181) | 29.95 percentage of HOMA2 | Standard Error 4.61 |
| LY2189265 0.75 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S, 52 weeks (n=175,181) | -2.66 percentage of HOMA2 | Standard Error 1.19 |
| LY2189265 0.75 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B, 78 weeks (n=167, 165) | 15.66 percentage of HOMA2 | Standard Error 4.75 |
| LY2189265 0.75 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B, 52 weeks (n=175, 181) | 24.60 percentage of HOMA2 | Standard Error 4.51 |
| LY2189265 0.75 mg | Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S, 78 weeks (n=167, 165) | -3.62 percentage of HOMA2 | Standard Error 1.23 |
Secondary
Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate
Sitting pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable sitting pulse rate data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 52 weeks (n=250, 252, 240) | 1.29 beats per minute (bpm) | Standard Error 0.5 |
| LY2189265 1.5 mg | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 26 weeks (n=257, 260, 245) | 1.56 beats per minute (bpm) | Standard Error 0.49 |
| LY2189265 1.5 mg | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 78 weeks (n=246, 244, 238) | 1.31 beats per minute (bpm) | Standard Error 0.5 |
| LY2189265 0.75 mg | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 52 weeks (n=250, 252, 240) | 0.51 beats per minute (bpm) | Standard Error 0.49 |
| LY2189265 0.75 mg | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 26 weeks (n=257, 260, 245) | 0.74 beats per minute (bpm) | Standard Error 0.48 |
| LY2189265 0.75 mg | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 78 weeks (n=246, 244, 238) | 0.61 beats per minute (bpm) | Standard Error 0.5 |
| Insulin Glargine | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 26 weeks (n=257, 260, 245) | -1.21 beats per minute (bpm) | Standard Error 0.5 |
| Insulin Glargine | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 78 weeks (n=246, 244, 238) | -0.91 beats per minute (bpm) | Standard Error 0.51 |
| Insulin Glargine | Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate | 52 weeks (n=250, 252, 240) | -0.52 beats per minute (bpm) | Standard Error 0.51 |
Secondary
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks
Number of participants achieving HbA1c levels less than 7.0% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model.
Time frame: 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 52 weeks (n=263, 267, 259) | 140 participants |
| LY2189265 1.5 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 26 weeks (n=263, 266, 258) | 153 participants |
| LY2189265 1.5 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 78 weeks (n=263, 267, 259) | 129 participants |
| LY2189265 0.75 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 52 weeks (n=263, 267, 259) | 99 participants |
| LY2189265 0.75 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 26 weeks (n=263, 266, 258) | 122 participants |
| LY2189265 0.75 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 78 weeks (n=263, 267, 259) | 91 participants |
| Insulin Glargine | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 26 weeks (n=263, 266, 258) | 84 participants |
| Insulin Glargine | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 78 weeks (n=263, 267, 259) | 79 participants |
| Insulin Glargine | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks | 52 weeks (n=263, 267, 259) | 80 participants |
p-value: <0.00195% CI: [2.98, 7.11]Regression, Logistic
p-value: <0.00195% CI: [1.41, 3.24]Regression, Logistic
p-value: <0.00195% CI: [2.45, 5.75]Regression, Logistic
p-value: 0.09895% CI: [0.94, 2.15]Regression, Logistic
p-value: <0.00195% CI: [1.85, 4.14]Regression, Logistic
p-value: 0.33495% CI: [0.82, 1.82]Regression, Logistic
Secondary
Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks
Number of participants achieving HbA1c levels less than or equal to 6.5% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model.
Time frame: 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 52 weeks (n=263, 267, 259) | 71 participants |
| LY2189265 1.5 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 26 weeks (n=263, 266, 258) | 97 participants |
| LY2189265 1.5 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 78 weeks (n=263, 267, 259) | 74 participants |
| LY2189265 0.75 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 52 weeks (n=263, 267, 259) | 60 participants |
| LY2189265 0.75 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 26 weeks (n=263, 266, 258) | 74 participants |
| LY2189265 0.75 mg | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 78 weeks (n=263, 267, 259) | 59 participants |
| Insulin Glargine | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 26 weeks (n=263, 266, 258) | 40 participants |
| Insulin Glargine | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 78 weeks (n=263, 267, 259) | 43 participants |
| Insulin Glargine | Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks | 52 weeks (n=263, 267, 259) | 35 participants |
p-value: <0.00195% CI: [2.9, 7.63]Regression, Logistic
p-value: <0.00195% CI: [1.57, 4.11]Regression, Logistic
p-value: <0.00195% CI: [1.81, 4.85]Regression, Logistic
p-value: 0.00495% CI: [1.26, 3.39]Regression, Logistic
p-value: <0.00195% CI: [1.44, 3.57]Regression, Logistic
p-value: 0.07395% CI: [0.96, 2.42]Regression, Logistic
Secondary
Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks
Additional intervention was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. The number of participants requiring additional intervention due to hyperglycemia is summarized cumulatively at 26, 52, and 78 weeks.
Time frame: 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 52 weeks | 11 participants |
| LY2189265 1.5 mg | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 26 weeks | 2 participants |
| LY2189265 1.5 mg | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 78 weeks | 24 participants |
| LY2189265 0.75 mg | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 52 weeks | 20 participants |
| LY2189265 0.75 mg | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 26 weeks | 4 participants |
| LY2189265 0.75 mg | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 78 weeks | 34 participants |
| Insulin Glargine | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 26 weeks | 0 participants |
| Insulin Glargine | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 78 weeks | 16 participants |
| Insulin Glargine | Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks | 52 weeks | 8 participants |
Secondary
Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks
Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with adjudicated CV events is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 78 week | 0 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 52 weeks | 3 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 26 weeks | 2 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 78 week | 3 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 52 weeks | 0 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 26 weeks | 2 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 78 week | 3 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 52 weeks | 3 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 26 weeks | 0 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 78 week | 6 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 52 weeks | 0 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 52 weeks | 4 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 78 week | 6 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 78 week | 1 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 26 weeks | 1 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 26 weeks | 0 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 26 weeks | 1 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 52 weeks | 4 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 78 week | 9 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 52 weeks | 1 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 26 weeks | 0 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 52 weeks | 5 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 52 weeks | 6 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 78 week | 8 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any fatal CV event, 78 week | 1 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any non-fatal CV event, 26 weeks | 3 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks | Any CV event, 26 weeks | 3 participants |
Secondary
Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks
The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 52 weeks | 2 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 26 weeks | 1 participants |
| LY2189265 1.5 mg | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 78 weeks | 2 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 52 weeks | 1 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 26 weeks | 1 participants |
| LY2189265 0.75 mg | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 78 weeks | 1 participants |
| Insulin Glargine | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 26 weeks | 0 participants |
| Insulin Glargine | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 78 weeks | 0 participants |
| Insulin Glargine | Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks | 52 weeks | 0 participants |
Secondary
Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum)
LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed at baseline, 26, 52, and 78 weeks, and at the safety follow-up visit 30 days after study drug discontinuation (83 weeks). The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA at each time point were summarized.
Time frame: Baseline, 26, 52, 78, and 83 weeks
Population: Participants who received at least one dose of LY2189265 with evaluable LY2189265 ADA data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) | 26 weeks | 11 participants |
| LY2189265 1.5 mg | Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) | 52 weeks | 3 participants |
| LY2189265 1.5 mg | Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) | 78 weeks | 1 participants |
| LY2189265 1.5 mg | Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum) | 83 weeks | 0 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks
A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine. The number of participants with at least 1 TEAE is reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 52 weeks | 189 participants |
| LY2189265 1.5 mg | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 26 weeks | 160 participants |
| LY2189265 1.5 mg | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 78 weeks | 201 participants |
| LY2189265 0.75 mg | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 52 weeks | 175 participants |
| LY2189265 0.75 mg | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 26 weeks | 146 participants |
| LY2189265 0.75 mg | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 78 weeks | 188 participants |
| Insulin Glargine | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 26 weeks | 137 participants |
| Insulin Glargine | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 78 weeks | 192 participants |
| Insulin Glargine | Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks | 52 weeks | 175 participants |
Secondary
Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 78 weeks | 607 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 52 weeks | 185 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 78 weeks | 2 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 26 weeks | 500 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 52 weeks | 1 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 26 weeks | 145 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 52 weeks | 757 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 26 weeks | 11 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 78 weeks | 884 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 26 weeks | 311 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 78 weeks | 20 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 26 weeks | 1 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 52 weeks | 515 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 52 weeks | 17 events |
| LY2189265 1.5 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 78 weeks | 215 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 78 weeks | 184 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 26 weeks | 0 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 52 weeks | 0 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 78 weeks | 0 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 26 weeks | 315 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 52 weeks | 444 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 78 weeks | 515 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 26 weeks | 484 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 52 weeks | 709 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 78 weeks | 911 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 26 weeks | 117 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 52 weeks | 147 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 26 weeks | 19 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 52 weeks | 24 events |
| LY2189265 0.75 mg | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 78 weeks | 28 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 78 weeks | 1033 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 52 weeks | 22 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 52 weeks | 519 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 52 weeks | 789 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 26 weeks | 447 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 78 weeks | 635 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 78 weeks | 2 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 26 weeks | 1 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 26 weeks | 20 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 52 weeks | 1093 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 52 weeks | 2 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 78 weeks | 1358 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 26 weeks | 609 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 78 weeks | 26 events |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 26 weeks | 240 events |
Secondary
Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 26, 52, and 78 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26, 52, and 78 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 78 weeks | 0.77 events per participant per year | Standard Deviation 2.97 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 26 weeks | 3.79 events per participant per year | Standard Deviation 8.01 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 78 weeks | 0.05 events per participant per year | Standard Deviation 0.32 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 52 weeks | 0.90 events per participant per year | Standard Deviation 3.13 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 52 weeks | 3.08 events per participant per year | Standard Deviation 6.97 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 26 weeks | 2.35 events per participant per year | Standard Deviation 5.41 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 26 weeks | 1.23 events per participant per year | Standard Deviation 3.84 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 78 weeks | 2.56 events per participant per year | Standard Deviation 5.9 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 26 weeks | 0.01 events per participant per year | Standard Deviation 0.12 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 52 weeks | 0.07 events per participant per year | Standard Deviation 0.4 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 52 weeks | 2.03 events per participant per year | Standard Deviation 4.16 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 78 weeks | 0.01 events per participant per year | Standard Deviation 0.06 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 26 weeks | 0.08 events per participant per year | Standard Deviation 0.59 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 78 weeks | 1.67 events per participant per year | Standard Deviation 3.58 |
| LY2189265 1.5 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 52 weeks | 0.00 events per participant per year | Standard Deviation 0.06 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 26 weeks | 0.00 events per participant per year | Standard Deviation 0 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 52 weeks | 0.00 events per participant per year | Standard Deviation 0 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 78 weeks | 0.00 events per participant per year | Standard Deviation 0 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 26 weeks | 2.52 events per participant per year | Standard Deviation 6.42 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 52 weeks | 1.97 events per participant per year | Standard Deviation 5.31 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 78 weeks | 1.66 events per participant per year | Standard Deviation 4.96 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 26 weeks | 3.58 events per participant per year | Standard Deviation 7.7 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 52 weeks | 2.68 events per participant per year | Standard Deviation 5.4 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 78 weeks | 2.38 events per participant per year | Standard Deviation 4.95 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 26 weeks | 0.96 events per participant per year | Standard Deviation 3.53 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 52 weeks | 0.65 events per participant per year | Standard Deviation 2.65 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 78 weeks | 0.59 events per participant per year | Standard Deviation 2.47 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 26 weeks | 0.14 events per participant per year | Standard Deviation 1.39 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 52 weeks | 0.09 events per participant per year | Standard Deviation 0.99 |
| LY2189265 0.75 mg | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 78 weeks | 0.07 events per participant per year | Standard Deviation 0.67 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 52 weeks | 2.07 events per participant per year | Standard Deviation 4.67 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 78 weeks | 3.03 events per participant per year | Standard Deviation 5.63 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 26 weeks | 0.01 events per participant per year | Standard Deviation 0.12 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 78 weeks | 1.81 events per participant per year | Standard Deviation 4.12 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 52 weeks | 3.34 events per participant per year | Standard Deviation 5.91 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 78 weeks | 0.07 events per participant per year | Standard Deviation 0.37 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 26 weeks | 0.15 events per participant per year | Standard Deviation 0.87 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Documented symptomatic HE, 26 weeks | 3.64 events per participant per year | Standard Deviation 6.63 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 52 weeks | 0.01 events per participant per year | Standard Deviation 0.09 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 78 weeks | 3.80 events per participant per year | Standard Deviation 7.24 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 52 weeks | 4.41 events per participant per year | Standard Deviation 8.72 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Probable symptomatic HE, 52 weeks | 0.08 events per participant per year | Standard Deviation 0.47 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Nocturnal HE, 26 weeks | 1.86 events per participant per year | Standard Deviation 4.84 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Asymptomatic HE, 26 weeks | 4.82 events per participant per year | Standard Deviation 11.43 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks | Severe HE, 78 weeks | 0.01 events per participant per year | Standard Deviation 0.06 |