Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of LY2189265 in comparison to Insulin Glargine, both in combination with Insulin Lispro (plus or minus Metformin), in participants with Type 2 Diabetes treated with 1 or 2 injections of insulin.
Detailed description
The term rescue therapy in this trial was defined as therapy for participants who met criteria for persistent severe hyperglycemia and therapy for participants who required new intervention for any other reason. The latter included participants who discontinued study drug due to adverse events, participant decision, or any other reason. For efficacy analyses, participants who received rescue medication were included in the analysis population, but only measurements obtained prior to taking rescue therapy were included in the efficacy analysis. For safety analyses, with the exception of hypoglycemia, all measurements including those obtained after taking rescue therapy were included in the analysis.
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 * Currently using insulin for at least 3 months with a conventional insulin regimen with or without oral medications * Glycosylated hemoglobin (HbA1c) greater than or equal to 7% and less than or equal to 11% * Willing to inject subcutaneous medication * Willing to monitor blood glucose levels and adjust insulin dose * Willing to maintain a study diary * Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m\^2) * Stable weight for 3 months prior to screening * Females of child bearing potential must test negative for pregnancy at screening 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 * Previous therapy with glucagon-like peptide 1 (GLP-1) agonists within 3 months prior to screening * 1 or more episodes of ketoacidosis within 6 months prior to screening * Have been treated with prescription or over the counter medication to promote weight loss within 3 months prior to screening * Estimated glomerular filtration rate (eGFR) less than or equal to 30 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) at screening * Taking steroids for greater than 14 days except for topical, eye, nasal, or inhaled * History of heart failure, New York Heart Classification III or IV within 2 months prior to screening * Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking medications that directly affect GI motility * Acute or chronic hepatitis or pancreatitis * Self or family history of 2A or type 2B multiple endocrine neoplasia or medullary C-Cell hyperplasia * Serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/mL) at screening * Organ transplant except cornea * Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis * History of or active malignancy except skin or in situ cervical or prostate cancer within the last 5 years * Known drug or alcohol abuse * Have enrolled in another clinical trial within the last 30 days * Have previously signed an informed consent or participated in a LY2189265 study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 26 weeks | Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | 26 weeks and 52 weeks | The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model. |
| Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia | Baseline, 26 weeks, and 52 weeks | The percentage of participants achieving HbA1c less than 7.0% without nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking) or severe (episodes requiring the assistance of another person to actively administer resuscitative actions) hypoglycemia was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model. |
| Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Baseline, 26 weeks, and 52 weeks | The self-monitored plasma glucose (SMPG) 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 3AM or 5 hours after bedtime. The mean of the 8 time points (Daily Mean) was also calculated. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, metformin, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose | Baseline, 26 weeks, and 52 weeks | Fasting serum glucose was measured by the central laboratory. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline fasting blood glucose as a covariate. |
| Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Baseline and 26 weeks and 52 weeks | Total daily insulin (TDI) dose was reported at baseline, 26 weeks, and 52 weeks. Daily Insulin Lispro and Insulin Glargine doses were reported at 26 and 52 weeks. |
| Change From Baseline to 26 and 52 Weeks in Body Weight | Baseline, 26 weeks, and 52 weeks | Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline body weight as a covariate. |
| Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline and 52 weeks and 4 weeks after last dose | — |
| Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | Baseline, 26 weeks, and 52 weeks | Body mass index 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline BMI as a covariate. |
| Change From Baseline to 26 and 52 Weeks in the EQ-5D | Baseline, 26 weeks, and 52 weeks | The 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 consists of a 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) adjusted by treatment, country, metformin use, and baseline. |
| Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) | Baseline, 26 weeks, and 52 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, treatment, and metformin use as fixed effects and baseline score as a covariate. |
| Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) | Baseline, 26 weeks, and 52 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, treatment, and metformin use as fixed effects and baseline score as a covariate. |
| Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) | Baseline, 26 weeks, and 52 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, treatment and metformin use as fixed effects and baseline score as a covariate. |
| Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Baseline, 26 weeks, and 52 weeks | Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured. |
| Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline and 52 weeks and 4 weeks after last dose | Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured at baseline and at 4 weeks after last dose (ALD). |
| Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 52 weeks | Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c. |
| Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline and 52 weeks and 4 weeks after last dose | — |
| Change From Baseline to 26 and 52 Weeks in Blood Pressure | Baseline, 26 weeks, and 52 weeks | Seated systolic blood pressure (SBP) and seated 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline blood pressure as a covariate. |
| Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline and 52 weeks and 4 weeks after last dose | Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured. |
| Change From Baseline to 26 and 52 Weeks in Pulse Rate | Baseline, 26 weeks, and 52 weeks | Seated 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline as a covariate |
| Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline and 52 weeks and 4 weeks after last dose | Seated pulse rate was measured. |
| Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | Baseline, 26 weeks, and 52 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline value as a covariate. |
| Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | Baseline, 26 weeks, and 52 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline value as a covariate. |
| Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Baseline through 52 weeks | The number of adjudicated (by an independent Clinical Endpoint Committee \[CEC\]) pancreatic events is summarized at 52 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 With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Baseline through 26 weeks and 52 weeks | Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions and had a plasma glucose \[PG\] of ≤ 70 milligrams per deciliter \[mg/dL\]), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG of ≤ 70 mg/dL), or asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL). The number of participants with self-reported hypoglycemic events is summarized cumulatively. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Baseline through 52 weeks | Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions and had a plasma glucose \[PG\] of ≤ 70 milligrams per deciliter \[mg/dL\]), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG of ≤ 70 mg/dL), or asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 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 With Adjudicated Cardiovascular Events up to 52 Weeks | Baseline through 52 weeks | 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. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Baseline through 4 weeks after last dose | A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. |
| Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Baseline through 26 weeks, 52 weeks, and 4 weeks after last dose | 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 weeks, 52 weeks, and 4 weeks after last dose. 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 and 52 Weeks in Serum Calcitonin | Baseline, 26 weeks, and 52 weeks | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Denmark, Greece, Hungary, Mexico, Poland, Puerto Rico, Russia, Spain, Sweden, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks | 295 |
| 0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks | 293 |
| Insulin Glargine Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 52 weeks
Insulin Lispro: dose titration based on blood glucose measures, subcutaneous (SC), thrice daily (after each meal) for 52 weeks | 296 |
| Total | 884 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 21 | 13 | 8 |
| Overall Study | Death | 0 | 1 | 3 |
| Overall Study | Entry Criteria Not Met | 3 | 1 | 1 |
| Overall Study | Lost to Follow-up | 8 | 5 | 9 |
| Overall Study | Physician Decision | 6 | 8 | 9 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | Sponsor Decision | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 19 | 25 | 21 |
Baseline characteristics
| Characteristic | Insulin Glargine | 1.5 mg LY2189265 | 0.75 mg LY2189265 | Total |
|---|---|---|---|---|
| Age, Continuous | 59.90 years STANDARD_DEVIATION 9.08 | 58.88 years STANDARD_DEVIATION 9.55 | 59.31 years STANDARD_DEVIATION 8.98 | 59.36 years STANDARD_DEVIATION 9.21 |
| Body Mass Index (BMI) | 32.41 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.33 | 31.99 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.11 | 33.08 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.15 | 32.49 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.21 |
| Body Weight | 90.75 kilograms (kg) STANDARD_DEVIATION 18.87 | 91.00 kilograms (kg) STANDARD_DEVIATION 18.24 | 91.69 kilograms (kg) STANDARD_DEVIATION 18.03 | 91.14 kilograms (kg) STANDARD_DEVIATION 18.37 |
| Duration of Diabetes | 12.96 years STANDARD_DEVIATION 6.8 | 12.80 years STANDARD_DEVIATION 7.19 | 12.43 years STANDARD_DEVIATION 6.92 | 12.73 years STANDARD_DEVIATION 6.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 100 Participants | 102 Participants | 101 Participants | 303 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 196 Participants | 193 Participants | 192 Participants | 581 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Glycosylated Hemoglobin (HbA1c) | 8.53 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.03 | 8.46 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.08 | 8.40 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.03 | 8.46 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.05 |
| Race (NIH/OMB) American Indian or Alaska Native | 17 Participants | 16 Participants | 13 Participants | 46 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 9 Participants | 12 Participants | 35 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 32 Participants | 27 Participants | 85 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 7 Participants | 6 Participants | 20 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 231 Participants | 231 Participants | 235 Participants | 697 Participants |
| Region of Enrollment Argentina | 28 participants | 26 participants | 27 participants | 81 participants |
| Region of Enrollment Australia | 8 participants | 10 participants | 8 participants | 26 participants |
| Region of Enrollment Belgium | 4 participants | 5 participants | 5 participants | 14 participants |
| Region of Enrollment Brazil | 32 participants | 33 participants | 30 participants | 95 participants |
| Region of Enrollment Canada | 9 participants | 9 participants | 8 participants | 26 participants |
| Region of Enrollment Denmark | 4 participants | 4 participants | 4 participants | 12 participants |
| Region of Enrollment Greece | 8 participants | 8 participants | 7 participants | 23 participants |
| Region of Enrollment Hungary | 19 participants | 19 participants | 19 participants | 57 participants |
| Region of Enrollment Mexico | 17 participants | 19 participants | 19 participants | 55 participants |
| Region of Enrollment Poland | 14 participants | 13 participants | 13 participants | 40 participants |
| Region of Enrollment Puerto Rico | 18 participants | 13 participants | 20 participants | 51 participants |
| Region of Enrollment Russian Federation | 9 participants | 6 participants | 8 participants | 23 participants |
| Region of Enrollment Spain | 9 participants | 8 participants | 10 participants | 27 participants |
| Region of Enrollment Sweden | 12 participants | 11 participants | 11 participants | 34 participants |
| Region of Enrollment Taiwan | 9 participants | 8 participants | 9 participants | 26 participants |
| Region of Enrollment United States | 96 participants | 103 participants | 95 participants | 294 participants |
| Sex: Female, Male Female | 131 Participants | 135 Participants | 145 Participants | 411 Participants |
| Sex: Female, Male Male | 165 Participants | 160 Participants | 148 Participants | 473 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 | 219 / 295 | 232 / 293 | 203 / 296 |
| serious Total, serious adverse events | 27 / 295 | 46 / 293 | 53 / 296 |
Outcome results
Primary
Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.
Time frame: Baseline, 26 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 |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.64 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| 0.75 mg LY2189265 | Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.59 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| Insulin Glargine | Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.41 percentage of glycosylated hemoglobin | Standard Error 0.07 |
Comparison: The study was designed to enroll 837 randomized participants (279 per treatment arm) with 90% power to detect non-inferiority of 1.5 mg LY2189265 versus Insulin Glargine on HbA1c change from baseline at the 26-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 248 participants per arm, with an assumed drop-out rate of 11%.p-value: <0.00195% CI: [-0.38, -0.07]ANCOVA
p-value: <0.00195% CI: [-0.33, -0.02]ANCOVA
Comparison: Superiority analysis.p-value: 0.00595% CI: [-0.38, -0.07]ANCOVA
Comparison: Superiority analysis.p-value: 0.01595% CI: [-0.33, -0.02]ANCOVA
Secondary
Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured.
Time frame: Baseline and 52 weeks and 4 weeks after last dose
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 (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, Baseline | 133.26 milliliters of mercury (mmHg) | Standard Deviation 16.56 |
| 1.5 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, Baseline | 77.33 milliliters of mercury (mmHg) | Standard Deviation 9.73 |
| 1.5 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, 4 weeks after last dose (n=260, 260, 255) | 76.58 milliliters of mercury (mmHg) | Standard Deviation 10.06 |
| 1.5 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, 52 weeks (n=290, 290, 295) | 132.67 milliliters of mercury (mmHg) | Standard Deviation 15.4 |
| 1.5 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, 4 weeks after last dose (n=260, 260, 255) | 133.77 milliliters of mercury (mmHg) | Standard Deviation 16.8 |
| 1.5 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, 52 weeks (n=290, 290, 295) | 77.33 milliliters of mercury (mmHg) | Standard Deviation 9.63 |
| 0.75 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, 4 weeks after last dose (n=260, 260, 255) | 77.04 milliliters of mercury (mmHg) | Standard Deviation 9.6 |
| 0.75 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, Baseline | 134.03 milliliters of mercury (mmHg) | Standard Deviation 15.87 |
| 0.75 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, 52 weeks (n=290, 290, 295) | 134.31 milliliters of mercury (mmHg) | Standard Deviation 16.41 |
| 0.75 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, 52 weeks (n=290, 290, 295) | 77.59 milliliters of mercury (mmHg) | Standard Deviation 9.74 |
| 0.75 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, 4 weeks after last dose (n=260, 260, 255) | 134.72 milliliters of mercury (mmHg) | Standard Deviation 16.5 |
| 0.75 mg LY2189265 | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, Baseline | 77.57 milliliters of mercury (mmHg) | Standard Deviation 9 |
| Insulin Glargine | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, 52 weeks (n=290, 290, 295) | 77.07 milliliters of mercury (mmHg) | Standard Deviation 9.92 |
| Insulin Glargine | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, 4 weeks after last dose (n=260, 260, 255) | 132.75 milliliters of mercury (mmHg) | Standard Deviation 16.01 |
| Insulin Glargine | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, Baseline | 133.26 milliliters of mercury (mmHg) | Standard Deviation 16.97 |
| Insulin Glargine | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, Baseline | 77.18 milliliters of mercury (mmHg) | Standard Deviation 10.41 |
| Insulin Glargine | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | DBP, 4 weeks after last dose (n=260, 260, 255) | 76.94 milliliters of mercury (mmHg) | Standard Deviation 9.1 |
| Insulin Glargine | Blood Pressure at Baseline, 52 Weeks, and 4 Weeks After Last Dose | SBP, 52 weeks (n=290, 290, 295) | 134.90 milliliters of mercury (mmHg) | Standard Deviation 16.25 |
Secondary
Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Time frame: Baseline and 52 weeks and 4 weeks after last dose
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable body weight data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=259, 260, 253) | 91.69 kilograms (kg) | Standard Deviation 18.6 |
| 1.5 mg LY2189265 | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 91.00 kilograms (kg) | Standard Deviation 18.24 |
| 1.5 mg LY2189265 | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=290, 290, 295) | 91.58 kilograms (kg) | Standard Deviation 19.06 |
| 0.75 mg LY2189265 | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=259, 260, 253) | 93.14 kilograms (kg) | Standard Deviation 19.2 |
| 0.75 mg LY2189265 | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 91.69 kilograms (kg) | Standard Deviation 18.03 |
| 0.75 mg LY2189265 | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=290, 290, 295) | 93.21 kilograms (kg) | Standard Deviation 19.23 |
| Insulin Glargine | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=259, 260, 253) | 94.27 kilograms (kg) | Standard Deviation 20.13 |
| Insulin Glargine | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 90.75 kilograms (kg) | Standard Deviation 18.87 |
| Insulin Glargine | Body Weight at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=290, 290, 295) | 94.14 kilograms (kg) | Standard Deviation 19.72 |
Secondary
Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles
The self-monitored plasma glucose (SMPG) 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 3AM or 5 hours after bedtime. The mean of the 8 time points (Daily Mean) was also calculated. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, metformin, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable SMPG data. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-midday meal, 52 weeks (n=202, 210, 212) | -4.33 millimoles per liter (mmol/L)] | Standard Error 0.18 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Bedtime, 52 weeks (n=195, 205, 213) | -3.62 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Bedtime, 26 weeks (n=220, 221, 226) | -4.00 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-evening meal, 26 weeks (n=226, 231, 232) | -3.24 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-morning meal, 26 weeks (n=228, 231, 232) | -0.36 millimoles per liter (mmol/L)] | Standard Error 0.14 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-morning meal, 26 weeks (n=220, 227, 229) | -3.70 millimoles per liter (mmol/L)] | Standard Error 0.19 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-midday meal, 26 weeks (n=227, 231, 233) | -2.80 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Daily Mean, 26 weeks (n=202, 206, 199) | -3.17 millimoles per liter (mmol/L)] | Standard Error 0.12 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | After bedtime, 52 weeks (n=192, 192 197) | -1.17 millimoles per liter (mmol/L)] | Standard Error 0.15 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-evening meal, 52 weeks (n=200, 210, 212) | -4.22 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-morning meal, 52 weeks (n=207, 213, 218) | 0.03 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-evening meal, 26 weeks (n=220, 228, 227) | -4.61 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Daily Mean, 52 weeks (n=182, 185, 189) | -2.84 millimoles per liter (mmol/L)] | Standard Error 0.12 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-morning meal, 52 weeks (n=200, 211, 211) | -3.38 millimoles per liter (mmol/L)] | Standard Error 0.19 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-evening meal, 52 weeks (n=207, 214, 217) | 3.00 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-midday meal, 26 weeks (n=219, 227, 228) | -4.51 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-midday meal, 52 weeks (n=207, 213, 218) | -2.53 millimoles per liter (mmol/L)] | Standard Error 0.14 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | After bedtime, 26 weeks (n=208, 216, 208) | -1.48 millimoles per liter (mmol/L)] | Standard Error 0.15 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-midday meal, 52 weeks (n=207, 213, 218) | -2.52 millimoles per liter (mmol/L)] | Standard Error 0.14 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-midday meal, 52 weeks (n=202, 210, 212) | -4.29 millimoles per liter (mmol/L)] | Standard Error 0.18 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-evening meal, 52 weeks (n=207, 214, 217) | -3.07 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-evening meal, 52 weeks (n=200, 210, 212) | -4.54 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-evening meal, 26 weeks (n=226, 231, 232) | -3.06 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Bedtime, 52 weeks (n=195, 205, 213) | -3.96 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | After bedtime, 52 weeks (n=192, 192 197) | -1.36 millimoles per liter (mmol/L)] | Standard Error 0.15 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Daily Mean, 52 weeks (n=182, 185, 189) | -2.95 millimoles per liter (mmol/L)] | Standard Error 0.12 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-evening meal, 26 weeks (n=220, 228, 227) | -4.54 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-morning meal, 26 weeks (n=220, 227, 229) | -3.29 millimoles per liter (mmol/L)] | Standard Error 0.19 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Bedtime, 26 weeks (n=220, 221, 226) | -3.89 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | After bedtime, 26 weeks (n=208, 216, 208) | -1.50 millimoles per liter (mmol/L)] | Standard Error 0.15 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Daily Mean, 26 weeks (n=202, 206, 199) | -2.97 millimoles per liter (mmol/L)] | Standard Error 0.12 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-midday meal, 26 weeks (n=227, 231, 233) | -2.38 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-morning meal, 52 weeks (n=207, 213, 218) | 0.05 millimoles per liter (mmol/L)] | Standard Error 0.15 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-morning meal, 26 weeks (n=228, 231, 232) | -0.06 millimoles per liter (mmol/L)] | Standard Error 0.14 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-morning meal, 52 weeks (n=200, 211, 211) | -3.23 millimoles per liter (mmol/L)] | Standard Error 0.19 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-midday meal, 26 weeks (n=219, 227, 228) | -4.53 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Daily Mean, 52 weeks (n=182, 185, 189) | -2.97 millimoles per liter (mmol/L)] | Standard Error 0.12 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-morning meal, 26 weeks (n=228, 231, 232) | -2.01 millimoles per liter (mmol/L)] | Standard Error 0.14 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-morning meal, 26 weeks (n=220, 227, 229) | -4.03 millimoles per liter (mmol/L)] | Standard Error 0.18 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-midday meal, 26 weeks (n=227, 231, 233) | -2.65 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-midday meal, 26 weeks (n=219, 227, 228) | -3.70 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-evening meal, 26 weeks (n=226, 231, 232) | -2.74 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-evening meal, 26 weeks (n=220, 228, 227) | -3.90 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Bedtime, 26 weeks (n=220, 221, 226) | -3.40 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | After bedtime, 26 weeks (n=208, 216, 208) | -1.96 millimoles per liter (mmol/L)] | Standard Error 0.15 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Daily Mean, 26 weeks (n=202, 206, 199) | -3.10 millimoles per liter (mmol/L)] | Standard Error 0.12 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-morning meal, 52 weeks (n=207, 213, 218) | -2.02 millimoles per liter (mmol/L)] | Standard Error 0.15 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-morning meal, 52 weeks (n=200, 211, 211) | -3.76 millimoles per liter (mmol/L)] | Standard Error 0.19 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-midday meal, 52 weeks (n=207, 213, 218) | -2.63 millimoles per liter (mmol/L)] | Standard Error 0.14 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-midday meal, 52 weeks (n=202, 210, 212) | -3.83 millimoles per liter (mmol/L)] | Standard Error 0.18 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Pre-evening meal, 52 weeks (n=207, 214, 217) | -2.67 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Post-evening meal, 52 weeks (n=200, 210, 212) | -3.71 millimoles per liter (mmol/L)] | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Bedtime, 52 weeks (n=195, 205, 213) | -3.27 millimoles per liter (mmol/L)] | Standard Error 0.17 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | After bedtime, 52 weeks (n=192, 192 197) | -1.80 millimoles per liter (mmol/L)] | Standard Error 0.15 |
p-value: 0.62895% CI: [-0.35, 0.21]Mixed Models Analysis
p-value: 0.36895% CI: [-0.15, 0.41]Mixed Models Analysis
p-value: 0.3795% CI: [-0.16, 0.42]Mixed Models Analysis
p-value: 0.87995% CI: [-0.26, 0.3]Mixed Models Analysis
Secondary
Change From Baseline to 26 and 52 Weeks in Blood Pressure
Seated systolic blood pressure (SBP) and seated 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline blood pressure as a covariate.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 26 weeks (n=255, 261, 258) | 0.02 milliliters of mercury (mmHg) | Standard Error 0.56 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 52 weeks (n=239, 240, 246) | -0.26 milliliters of mercury (mmHg) | Standard Error 0.94 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 26 weeks (n=255, 261, 258) | -0.97 milliliters of mercury (mmHg) | Standard Error 0.88 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 52 weeks (n=239, 240, 246) | -0.01 milliliters of mercury (mmHg) | Standard Error 0.57 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 26 weeks (n=255, 261, 258) | -0.08 milliliters of mercury (mmHg) | Standard Error 0.56 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 26 weeks (n=255, 261, 258) | -0.65 milliliters of mercury (mmHg) | Standard Error 0.87 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 52 weeks (n=239, 240, 246) | 1.04 milliliters of mercury (mmHg) | Standard Error 0.93 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 52 weeks (n=239, 240, 246) | 0.15 milliliters of mercury (mmHg) | Standard Error 0.57 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 26 weeks (n=255, 261, 258) | 2.23 milliliters of mercury (mmHg) | Standard Error 0.88 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 26 weeks (n=255, 261, 258) | -0.23 milliliters of mercury (mmHg) | Standard Error 0.56 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 52 weeks (n=239, 240, 246) | -0.34 milliliters of mercury (mmHg) | Standard Error 0.56 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 52 weeks (n=239, 240, 246) | 1.98 milliliters of mercury (mmHg) | Standard Error 0.92 |
Secondary
Change From Baseline to 26 and 52 Weeks in Body Weight
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country, treatment, and metformin use as fixed effects and baseline body weight as a covariate.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable body weight 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 (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 26 weeks | -0.87 kilograms (kg) | Standard Error 0.27 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 52 weeks | -0.35 kilograms (kg) | Standard Error 0.34 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 26 weeks | 0.18 kilograms (kg) | Standard Error 0.27 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 52 weeks | 0.86 kilograms (kg) | Standard Error 0.33 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Body Weight | 26 weeks | 2.33 kilograms (kg) | Standard Error 0.27 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Body Weight | 52 weeks | 2.89 kilograms (kg) | Standard Error 0.33 |
p-value: <0.00195% CI: [-3.81, -2.59]ANCOVA
p-value: <0.00195% CI: [-2.76, -1.54]ANCOVA
p-value: <0.00195% CI: [-3.99, -2.48]ANCOVA
p-value: <0.00195% CI: [-2.78, -1.27]ANCOVA
Secondary
Change From Baseline to 26 and 52 Weeks in 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline value as a covariate.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=238, 243, 236) | 0.82 milliseconds (msec) | Standard Error 0.95 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=220, 222, 221) | 0.85 milliseconds (msec) | Standard Error 1 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n= 222, 221, 221) | 1.89 milliseconds (msec) | Standard Error 1.13 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=241, 242, 236) | 0.29 milliseconds (msec) | Standard Error 1.13 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=220, 222, 221) | 0.05 milliseconds (msec) | Standard Error 0.99 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n= 222, 221, 221) | 1.48 milliseconds (msec) | Standard Error 1.13 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=241, 242, 236) | 0.30 milliseconds (msec) | Standard Error 1.12 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=238, 243, 236) | -1.75 milliseconds (msec) | Standard Error 0.94 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n= 222, 221, 221) | 1.80 milliseconds (msec) | Standard Error 1.14 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=220, 222, 221) | -0.43 milliseconds (msec) | Standard Error 1 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=241, 242, 236) | 1.59 milliseconds (msec) | Standard Error 1.13 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=238, 243, 236) | -1.13 milliseconds (msec) | Standard Error 0.95 |
Secondary
Change From Baseline to 26 and 52 Weeks in 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline value as a covariate.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 26 weeks (n=244, 246, 243) | 3.95 beats per minute (bpm) | Standard Error 0.65 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 52 weeks (n=230, 226, 230) | 3.02 beats per minute (bpm) | Standard Error 0.67 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 26 weeks (n=244, 246, 243) | 4.18 beats per minute (bpm) | Standard Error 0.65 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 52 weeks (n=230, 226, 230) | 3.83 beats per minute (bpm) | Standard Error 0.67 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 26 weeks (n=244, 246, 243) | 1.37 beats per minute (bpm) | Standard Error 0.65 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 52 weeks (n=230, 226, 230) | 1.03 beats per minute (bpm) | Standard Error 0.67 |
Secondary
Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose
Fasting serum glucose was measured by the central laboratory. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, metformin use, and treatment-by-visit interaction as fixed effects and baseline fasting blood glucose as a covariate.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable fasting blood glucose data. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose | 26 weeks (n=253, 256, 255) | -0.27 millimoles per liter (mmol/L) | Standard Error 0.2 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose | 52 weeks (n=237, 238, 246) | 0.08 millimoles per liter (mmol/L) | Standard Error 0.22 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose | 26 weeks (n=253, 256, 255) | 0.22 millimoles per liter (mmol/L) | Standard Error 0.2 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose | 52 weeks (n=237, 238, 246) | 0.41 millimoles per liter (mmol/L) | Standard Error 0.22 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose | 26 weeks (n=253, 256, 255) | -1.58 millimoles per liter (mmol/L) | Standard Error 0.2 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Fasting Serum Glucose | 52 weeks (n=237, 238, 246) | -1.01 millimoles per liter (mmol/L) | Standard Error 0.22 |
p-value: <0.00195% CI: [0.83, 1.79]Mixed Models Analysis
p-value: <0.00195% CI: [1.32, 2.28]Mixed Models Analysis
p-value: <0.00195% CI: [0.55, 1.64]Mixed Models Analysis
p-value: <0.00195% CI: [0.88, 1.96]Mixed Models Analysis
Secondary
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured.
Time frame: Baseline, 26 weeks, and 52 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) |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 26 weeks (n=284, 282, 287) | 5.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 52 weeks (n=284, 283, 287) | 3.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 26 weeks (n=284, 282, 287) | 4.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 52 weeks (n=284, 283, 287) | 6.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 26 weeks (n=284, 282, 287) | 7.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 52 weeks (n=284, 283, 287) | 2.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 52 weeks (n=284, 283, 287) | 2.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 26 weeks (n=284, 282, 287) | 4.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 52 weeks (n=284, 283, 287) | 2.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 26 weeks (n=284, 282, 287) | 2.50 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 26 weeks (n=284, 282, 287) | 4.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 52 weeks (n=284, 283, 287) | 3.00 units per liter (U/L) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 26 weeks (n=284, 282, 287) | 1.00 units per liter (U/L) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 52 weeks (n=284, 283, 287) | -2.00 units per liter (U/L) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 26 weeks (n=284, 282, 287) | -2.00 units per liter (U/L) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 52 weeks (n=284, 283, 287) | 0.00 units per liter (U/L) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 26 weeks (n=284, 282, 287) | 1.00 units per liter (U/L) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 52 weeks (n=284, 283, 287) | 0.00 units per liter (U/L) |
Secondary
Change From Baseline to 26 and 52 Weeks in Pulse Rate
Seated 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline as a covariate
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable seated pulse rate data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 26 weeks (n=255, 261, 258) | 2.84 beats per minute (bpm) | Standard Error 0.57 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 52 weeks (n=239, 240, 246) | 2.38 beats per minute (bpm) | Standard Error 0.57 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 26 weeks (n=255, 261, 258) | 2.79 beats per minute (bpm) | Standard Error 0.56 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 52 weeks (n=239, 240, 246) | 2.27 beats per minute (bpm) | Standard Error 0.57 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 26 weeks (n=255, 261, 258) | 0.90 beats per minute (bpm) | Standard Error 0.56 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 52 weeks (n=239, 240, 246) | 0.93 beats per minute (bpm) | Standard Error 0.57 |
Secondary
Change From Baseline to 26 and 52 Weeks in Serum Calcitonin
Time frame: Baseline, 26 weeks, and 52 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 (MEDIAN) |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 26 weeks (n=283, 282, 285) | 0.00 picogram per milliliter (pcg/mL) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 52 weeks (n=283, 283, 285) | 0.00 picogram per milliliter (pcg/mL) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 26 weeks (n=283, 282, 285) | 0.00 picogram per milliliter (pcg/mL) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 52 weeks (n=283, 283, 285) | 0.00 picogram per milliliter (pcg/mL) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 52 weeks (n=283, 283, 285) | 0.00 picogram per milliliter (pcg/mL) |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 26 weeks (n=283, 282, 285) | 0.00 picogram per milliliter (pcg/mL) |
Secondary
Change From Baseline to 26 and 52 Weeks in the EQ-5D
The 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 consists of a 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) adjusted by treatment, country, metformin use, and baseline.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | VAS, 52 weeks (n=279, 278, 282) | -0.46 units on a scale | Standard Error 1.01 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | VAS, 26 weeks (n=278, 275, 275) | -1.69 units on a scale | Standard Error 1 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | EQ-5D UK, 26 weeks (n=272, 271, 274) | -0.03 units on a scale | Standard Error 0.01 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | EQ-5D UK, 52 weeks (n=274, 274, 281) | -0.04 units on a scale | Standard Error 0.01 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | EQ-5D UK, 26 weeks (n=272, 271, 274) | -0.03 units on a scale | Standard Error 0.01 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | EQ-5D UK, 52 weeks (n=274, 274, 281) | -0.04 units on a scale | Standard Error 0.01 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | VAS, 26 weeks (n=278, 275, 275) | -2.30 units on a scale | Standard Error 1 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the EQ-5D | VAS, 52 weeks (n=279, 278, 282) | -2.54 units on a scale | Standard Error 1.02 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the EQ-5D | VAS, 26 weeks (n=278, 275, 275) | -0.60 units on a scale | Standard Error 1 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the EQ-5D | EQ-5D UK, 26 weeks (n=272, 271, 274) | -0.03 units on a scale | Standard Error 0.01 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the EQ-5D | EQ-5D UK, 52 weeks (n=274, 274, 281) | -0.03 units on a scale | Standard Error 0.01 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the EQ-5D | VAS, 52 weeks (n=279, 278, 282) | -0.18 units on a scale | Standard Error 1.01 |
Secondary
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL)
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, treatment, and metformin use as fixed effects and baseline score as a covariate.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) | 26 weeks (n=274, 270, 270) | -0.50 units on a scale | Standard Error 0.3 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) | 52 weeks (n=277, 275, 279) | -0.50 units on a scale | Standard Error 0.33 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) | 26 weeks (n=274, 270, 270) | -0.60 units on a scale | Standard Error 0.31 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) | 52 weeks (n=277, 275, 279) | -1.05 units on a scale | Standard Error 0.33 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) | 26 weeks (n=274, 270, 270) | -0.93 units on a scale | Standard Error 0.31 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) | 52 weeks (n=277, 275, 279) | -1.28 units on a scale | Standard Error 0.33 |
Secondary
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP)
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, treatment, and metformin use as fixed effects and baseline score as a covariate.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) | 26 weeks (n=277, 274, 274) | 0.60 units on a scale | Standard Error 0.17 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) | 52 weeks (n=278, 277, 281) | 0.86 units on a scale | Standard Error 0.16 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) | 26 weeks (n=277, 274, 274) | 0.34 units on a scale | Standard Error 0.17 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) | 52 weeks (n=278, 277, 281) | 0.22 units on a scale | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) | 52 weeks (n=278, 277, 281) | 0.06 units on a scale | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) | 26 weeks (n=277, 274, 274) | 0.18 units on a scale | Standard Error 0.17 |
Secondary
Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS)
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, treatment and metformin use as fixed effects and baseline score as a covariate.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) | 26 weeks (n=251, 256, 250) | 3.75 units on a scale | Standard Error 1.31 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) | 52 weeks (n=234, 238, 244) | 2.51 units on a scale | Standard Error 1.25 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) | 26 weeks (n=251, 256, 250) | 2.91 units on a scale | Standard Error 1.29 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) | 52 weeks (n=234, 238, 244) | 0.92 units on a scale | Standard Error 1.23 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) | 26 weeks (n=251, 256, 250) | 2.83 units on a scale | Standard Error 1.3 |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Low Blood Sugar Survey (LBSS) | 52 weeks (n=234, 238, 244) | 2.38 units on a scale | Standard Error 1.23 |
Secondary
Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia
The percentage of participants achieving HbA1c less than 7.0% without nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking) or severe (episodes requiring the assistance of another person to actively administer resuscitative actions) hypoglycemia was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine. 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) |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia | 26 weeks | 53.8 percentage of participants |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia | 52 weeks | 44.0 percentage of participants |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia | 26 weeks | 54.5 percentage of participants |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia | 52 weeks | 44.0 percentage of participants |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia | 26 weeks | 28.2 percentage of participants |
| Insulin Glargine | Change From Baseline to 26 and 52 Weeks in the Percentage of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% Without Nocturnal or Severe Hypoglycemia | 52 weeks | 26.8 percentage of participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI)
Body mass index 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, metformin use, and treatment-by-visit interaction as fixed effects and baseline BMI as a covariate.
Time frame: Baseline, 26 weeks, and 52 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 |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 26 weeks (n=248, 251, 250) | -0.20 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 4 weeks after last dose | NA kilograms per meter squared (kg/m^2) | — |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 52 weeks (n=225, 224, 232) | 0.09 kilograms per meter squared (kg/m^2) | Standard Error 0.11 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 26 weeks (n=248, 251, 250) | 0.21 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 4 weeks after last dose | NA kilograms per meter squared (kg/m^2) | — |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 52 weeks (n=225, 224, 232) | 0.57 kilograms per meter squared (kg/m^2) | Standard Error 0.11 |
| Insulin Glargine | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 4 weeks after last dose | NA kilograms per meter squared (kg/m^2) | — |
| Insulin Glargine | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 52 weeks (n=225, 224, 232) | 1.33 kilograms per meter squared (kg/m^2) | Standard Error 0.11 |
| Insulin Glargine | Change From Baseline to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose in Body Mass Index (BMI) | 26 weeks (n=248, 251, 250) | 1.01 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
p-value: <0.00195% CI: [-1.44, -0.96]Mixed Models Analysis
p-value: <0.00195% CI: [-1.03, -0.55]Mixed Models Analysis
p-value: <0.00195% CI: [-1.55, -0.94]Mixed Models Analysis
p-value: <0.00195% CI: [-1.06, -0.46]Mixed Models Analysis
Secondary
Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, baseline metformin, and baseline HbA1c.
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 |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.48 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| 0.75 mg LY2189265 | Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.42 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| Insulin Glargine | Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.23 percentage of glycosylated hemoglobin | Standard Error 0.08 |
p-value: <0.00195% CI: [-0.42, -0.07]ANCOVA
p-value: <0.00195% CI: [-0.37, -0.02]ANCOVA
Comparison: Superiority analysis.p-value: 0.00595% CI: [-0.42, -0.07]ANCOVA
Comparison: Superiority analysis.p-value: 0.01495% CI: [-0.37, -0.02]ANCOVA
Secondary
Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose
The number of adjudicated (by an independent Clinical Endpoint Committee \[CEC\]) pancreatic events is summarized at 52 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 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks | 0 events |
| 1.5 mg LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 26 weeks | NA events |
| 1.5 mg LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose | NA events |
| 0.75 mg LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks | 0 events |
| 0.75 mg LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 26 weeks | NA events |
| 0.75 mg LY2189265 | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose | NA events |
| Insulin Glargine | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 26 weeks | NA events |
| Insulin Glargine | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose | NA events |
| Insulin Glargine | Number of Events of Adjudicated Pancreatitis up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks | 0 events |
Secondary
Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks
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. 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 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any non-fatal cardiovascular event | 5 participants |
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any fatal cardiovascular event | 0 participants |
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any cardiovascular event | 5 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any non-fatal cardiovascular event | 6 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any cardiovascular event | 6 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any fatal cardiovascular event | 0 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any non-fatal cardiovascular event | 11 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any fatal cardiovascular event | 2 participants |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular Events up to 52 Weeks | Any cardiovascular event | 12 participants |
Secondary
Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose
Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions and had a plasma glucose \[PG\] of ≤ 70 milligrams per deciliter \[mg/dL\]), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG of ≤ 70 mg/dL), or asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL). The number of participants with self-reported hypoglycemic events is summarized cumulatively. 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 weeks and 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 26 weeks | 228 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 52 weeks | 235 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 52 weeks | 191 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 26 weeks | 250 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 52 weeks | 252 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 26 weeks | 4 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 52 weeks | 8 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 4 weeks after last dose | NA participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 4 weeks after last dose | NA participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 26 weeks | 174 participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 4 weeks after last dose | NA participants |
| 1.5 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 4 weeks after last dose | NA participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 26 weeks | 5 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 4 weeks after last dose | NA participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 52 weeks | 7 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 4 weeks after last dose | NA participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 26 weeks | 242 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 52 weeks | 250 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 26 weeks | 258 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 4 weeks after last dose | NA participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 52 weeks | 263 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 52 weeks | 196 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 26 weeks | 179 participants |
| 0.75 mg LY2189265 | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 4 weeks after last dose | NA participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 26 weeks | 198 participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 4 weeks after last dose | NA participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 26 weeks | 9 participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 52 weeks | 14 participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 4 weeks after last dose | NA participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 4 weeks after last dose | NA participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Severe HE, 4 weeks after last dose | NA participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Asymptomatic HE, 52 weeks | 207 participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 26 weeks | 243 participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 52 weeks | 266 participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Documented Symptomatic HE, 52 weeks | 247 participants |
| Insulin Glargine | Number of Participants With Self-reported Hypoglycemic Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | Total HE, 26 weeks | 264 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose
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 weeks, 52 weeks, and 4 weeks after last dose. 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 weeks, 52 weeks, and 4 weeks after last dose
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks | 217 participants |
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose | 223 participants |
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 26 weeks | 203 participants |
| 0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose | 235 participants |
| 0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 26 weeks | 216 participants |
| 0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks | 230 participants |
| Insulin Glargine | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose | 211 participants |
| Insulin Glargine | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 26 weeks | 178 participants |
| Insulin Glargine | Number of Participants With Treatment Emergent Adverse Events up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks | 206 participants |
Secondary
Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose
A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.
Time frame: Baseline through 4 weeks after last dose
Population: Participants who received at least one dose of LY2189265 with evaluable LY2189265 ADA data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 26 weeks | NA participants |
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks | NA participants |
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent LY2189265 Antibodies up to 26 Weeks, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose | 9 participants |
Secondary
Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured at baseline and at 4 weeks after last dose (ALD).
Time frame: Baseline and 52 weeks and 4 weeks after last dose
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable pancreatic enzyme data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), Baseline | 61.21 units per liter (U/L) | Standard Deviation 27.89 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), 4 weeks ALD (n=251, 259, 251) | 61.69 units per liter (U/L) | Standard Deviation 28.06 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), Baseline | 26.56 units per liter (U/L) | Standard Deviation 14.51 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, 4 weeks ALD (n=252, 260, 251) | 44.19 units per liter (U/L) | Standard Deviation 36.92 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, Baseline | 41.42 units per liter (U/L) | Standard Deviation 34.19 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, 52 weeks (n=284, 283, 287) | 50.57 units per liter (U/L) | Standard Deviation 35.65 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), 52 weeks (n=284, 283, 287) | 66.08 units per liter (U/L) | Standard Deviation 30.29 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), 4 weeks ALD (n=251, 260, 251) | 27.50 units per liter (U/L) | Standard Deviation 15.49 |
| 1.5 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), 52 weeks (n=284, 283, 287) | 31.38 units per liter (U/L) | Standard Deviation 18.15 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), 4 weeks ALD (n=251, 260, 251) | 25.77 units per liter (U/L) | Standard Deviation 13.78 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, Baseline | 41.08 units per liter (U/L) | Standard Deviation 32.8 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, 52 weeks (n=284, 283, 287) | 45.34 units per liter (U/L) | Standard Deviation 31.23 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, 4 weeks ALD (n=252, 260, 251) | 41.86 units per liter (U/L) | Standard Deviation 25.22 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), 4 weeks ALD (n=251, 259, 251) | 59.21 units per liter (U/L) | Standard Deviation 30.32 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), Baseline | 58.59 units per liter (U/L) | Standard Deviation 23.19 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), Baseline | 25.10 units per liter (U/L) | Standard Deviation 13.48 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), 52 weeks (n=284, 283, 287) | 27.86 units per liter (U/L) | Standard Deviation 17.14 |
| 0.75 mg LY2189265 | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), 52 weeks (n=284, 283, 287) | 60.97 units per liter (U/L) | Standard Deviation 25.78 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, 4 weeks ALD (n=252, 260, 251) | 43.02 units per liter (U/L) | Standard Deviation 35.75 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), Baseline | 61.18 units per liter (U/L) | Standard Deviation 26.69 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), 52 weeks (n=284, 283, 287) | 61.93 units per liter (U/L) | Standard Deviation 27.12 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (total), 4 weeks ALD (n=251, 259, 251) | 62.13 units per liter (U/L) | Standard Deviation 26.11 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), Baseline | 26.43 units per liter (U/L) | Standard Deviation 15.94 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), 52 weeks (n=284, 283, 287) | 26.91 units per liter (U/L) | Standard Deviation 17.64 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Amylase (PD), 4 weeks ALD (n=251, 260, 251) | 26.84 units per liter (U/L) | Standard Deviation 15.44 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, Baseline | 43.20 units per liter (U/L) | Standard Deviation 37.35 |
| Insulin Glargine | Pancreatic Enzymes at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Lipase, 52 weeks (n=284, 283, 287) | 39.39 units per liter (U/L) | Standard Deviation 27.51 |
Secondary
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52
The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a repeated logistic regression model (generalized estimating equation model) with baseline HbA1c, baseline metformin, country, and treatment as factors included in the model.
Time frame: 26 weeks and 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 | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than or equal to 6.5%, 26 weeks | 48.0 percentage of participants |
| 1.5 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than 7.0%, 26 weeks | 67.6 percentage of participants |
| 1.5 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than or equal to 6.5%, 52 weeks | 36.7 percentage of participants |
| 1.5 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than 7.0%, 52 weeks | 58.5 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than or equal to 6.5%, 26 weeks | 43.0 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than 7.0%, 52 weeks | 56.3 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than 7.0%, 26 weeks | 69.0 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than or equal to 6.5%, 52 weeks | 34.7 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than or equal to 6.5%, 52 weeks | 30.4 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than 7.0%, 26 weeks | 56.8 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than 7.0%, 52 weeks | 49.3 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at Weeks 26 and 52 | HbA1c less than or equal to 6.5%, 26 weeks | 37.5 percentage of participants |
p-value: 0.014Regression, Logistic
p-value: 0.01Regression, Logistic
p-value: 0.027Regression, Logistic
p-value: 0.384Regression, Logistic
p-value: <0.05Regression, Logistic
p-value: 0.25Regression, Logistic
p-value: 0.272Regression, Logistic
p-value: 0.623Regression, Logistic
Secondary
Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Seated pulse rate was measured.
Time frame: Baseline and 52 weeks and 4 weeks after last dose
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable seated pulse rate data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 75.26 beats per minute (bpm) | Standard Deviation 11.03 |
| 1.5 mg LY2189265 | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=290, 290, 295) | 78.30 beats per minute (bpm) | Standard Deviation 11.01 |
| 1.5 mg LY2189265 | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=260, 260, 255) | 74.52 beats per minute (bpm) | Standard Deviation 11.09 |
| 0.75 mg LY2189265 | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=290, 290, 295) | 77.83 beats per minute (bpm) | Standard Deviation 10.9 |
| 0.75 mg LY2189265 | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=260, 260, 255) | 74.99 beats per minute (bpm) | Standard Deviation 11.98 |
| 0.75 mg LY2189265 | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 75.08 beats per minute (bpm) | Standard Deviation 11.1 |
| Insulin Glargine | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=290, 290, 295) | 76.02 beats per minute (bpm) | Standard Deviation 11.43 |
| Insulin Glargine | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=260, 260, 255) | 75.27 beats per minute (bpm) | Standard Deviation 11.17 |
| Insulin Glargine | Pulse Rate at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 74.54 beats per minute (bpm) | Standard Deviation 10.5 |
Secondary
Rate of Self-reported Hypoglycemic Events up to 52 Weeks
Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions and had a plasma glucose \[PG\] of ≤ 70 milligrams per deciliter \[mg/dL\]), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG of ≤ 70 mg/dL), or asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 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 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Total HE | 41.52 events per participant per year | Standard Deviation 46.51 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Severe HE | 0.03 events per participant per year | Standard Deviation 0.19 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Asymptomatic HE | 9.55 events per participant per year | Standard Deviation 19.52 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Documented Symptomatic HE | 30.98 events per participant per year | Standard Deviation 39.64 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Total HE | 47.42 events per participant per year | Standard Deviation 54.39 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Severe HE | 0.05 events per participant per year | Standard Deviation 0.5 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Documented Symptomatic HE | 35.03 events per participant per year | Standard Deviation 44.94 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Asymptomatic HE | 11.56 events per participant per year | Standard Deviation 24.69 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Total HE | 55.93 events per participant per year | Standard Deviation 59.46 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Asymptomatic HE | 14.20 events per participant per year | Standard Deviation 23.19 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Severe HE | 0.08 events per participant per year | Standard Deviation 0.43 |
| Insulin Glargine | Rate of Self-reported Hypoglycemic Events up to 52 Weeks | Documented Symptomatic HE | 39.90 events per participant per year | Standard Deviation 50.92 |
Secondary
Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose
Time frame: Baseline and 52 weeks and 4 weeks after last dose
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine with evaluable serum calcitonin data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=284, 283, 285) | 0.79 picomole per liter | Standard Deviation 0.89 |
| 1.5 mg LY2189265 | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 0.75 picomole per liter | Standard Deviation 0.78 |
| 1.5 mg LY2189265 | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=245, 254, 246) | 0.76 picomole per liter | Standard Deviation 0.87 |
| 0.75 mg LY2189265 | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=284, 283, 285) | 0.78 picomole per liter | Standard Deviation 0.9 |
| 0.75 mg LY2189265 | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 0.73 picomole per liter | Standard Deviation 0.77 |
| 0.75 mg LY2189265 | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=245, 254, 246) | 0.73 picomole per liter | Standard Deviation 0.72 |
| Insulin Glargine | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | Baseline | 0.78 picomole per liter | Standard Deviation 0.88 |
| Insulin Glargine | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 4 weeks after last dose (n=245, 254, 246) | 0.87 picomole per liter | Standard Deviation 0.95 |
| Insulin Glargine | Serum Calcitonin at Baseline, 52 Weeks, and 4 Weeks After Last Dose | 52 weeks (n=284, 283, 285) | 0.80 picomole per liter | Standard Deviation 0.89 |
Secondary
Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine)
Total daily insulin (TDI) dose was reported at baseline, 26 weeks, and 52 weeks. Daily Insulin Lispro and Insulin Glargine doses were reported at 26 and 52 weeks.
Time frame: Baseline and 26 weeks and 52 weeks
Population: Participants who were randomized and received at least one dose of LY2189265 or Insulin Glargine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, 26 weeks (n=244, 251, 254) | 93.24 units | Standard Deviation 78.02 |
| 1.5 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Lispro, 52 weeks (n=224, 227, 238) | 88.15 units | Standard Deviation 62.95 |
| 1.5 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Lispro, 26 weeks (n=244, 251, 254) | 93.24 units | Standard Deviation 78.02 |
| 1.5 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, Baseline | 55.20 units | Standard Deviation 32.17 |
| 1.5 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Glargine, 52 weeks (n=224, 227, 238) | NA units | — |
| 1.5 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Glargine, 26 weeks (n=244, 251, 254) | NA units | — |
| 1.5 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, 52 weeks (n=224, 227, 238) | 88.15 units | Standard Deviation 62.95 |
| 0.75 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Lispro, 26 weeks (n=244, 251, 254) | 96.69 units | Standard Deviation 62.13 |
| 0.75 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, Baseline | 59.11 units | Standard Deviation 38.12 |
| 0.75 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, 26 weeks (n=244, 251, 254) | 96.69 units | Standard Deviation 62.13 |
| 0.75 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, 52 weeks (n=224, 227, 238) | 95.00 units | Standard Deviation 67.62 |
| 0.75 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Lispro, 52 weeks (n=224, 227, 238) | 95.00 units | Standard Deviation 67.62 |
| 0.75 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Glargine, 26 weeks (n=244, 251, 254) | NA units | — |
| 0.75 mg LY2189265 | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Glargine, 52 weeks (n=224, 227, 238) | NA units | — |
| Insulin Glargine | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Lispro, 52 weeks (n=224, 227, 238) | 69.12 units | Standard Deviation 49.07 |
| Insulin Glargine | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, 26 weeks (n=244, 251, 254) | 132.00 units | Standard Deviation 79.01 |
| Insulin Glargine | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Glargine, 52 weeks (n=224, 227, 238) | 64.07 units | Standard Deviation 38.6 |
| Insulin Glargine | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Glargine, 26 weeks (n=244, 251, 254) | 64.48 units | Standard Deviation 40.23 |
| Insulin Glargine | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | Insulin Lispro, 26 weeks (n=244, 251, 254) | 67.79 units | Standard Deviation 44.59 |
| Insulin Glargine | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, 52 weeks (n=224, 227, 238) | 133.19 units | Standard Deviation 80.75 |
| Insulin Glargine | Total Daily Insulin Dose Overall and by Components (Insulin Lispro and Insulin Glargine) | TDI, Baseline | 53.93 units | Standard Deviation 30.67 |