Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to determine if LY2189265 is effective and safe in reducing hemoglobin A1c (HbA1c), as compared to placebo (no medicine), or exenatide in participants with Type 2 Diabetes. The participants must also be taking metformin and pioglitazone.
Detailed description
During the study, if a participant developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, the participant received additional therapeutic intervention or initiation of an alternative antihyperglycemic medication following study drug discontinuation (rescue therapy). Participants who received rescue therapy were included in the analysis population, but only measurements obtained prior to the beginning of rescue therapy were included in specified analyses.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 Diabetes (T2D) not well controlled on 1, 2, or 3 oral antidiabetic medications 1. Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication 2. HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications * Able to tolerate minimum dose of 1500 milligrams (mg) metformin a day and 30 mg pioglitazone per day. * Willing to inject subcutaneous (SC) medication up to 2 times per day * Stable weight for 3 months prior to screening * Body mass index (BMI) between 23 and 45 kilograms per meter squared (kg/m\^2) * Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug.
Exclusion criteria
* Type 1 Diabetes * HbA1c equal to or less than 6.5 before randomization or at randomization * Chronic insulin use * Taking drugs to promote weight loss by prescription or over the counter * Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled * History of fluid retention or edema * History of Heart Failure New York Heart Classification II, III, or IV or acute myocardial infarction or stroke within 2 months of screening * Gastrointestinal (GI; stomach) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility * Hepatitis or liver disease or alanine transaminase (ALT) greater than 2.5 times the upper limit of normal * Acute or chronic pancreatitis of any form * Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatine clearance of less than 60 milliliters per minute (mL/min) * History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer * A serum calcitonin greater than or equal to 20 picograms per milliliter (pg/mL) at screening * Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis * History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years * Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing * Organ transplant except cornea * Have enrolled in another clinical trial within the last 30 days * Have previously signed an informed consent or participated in a LY2189265 (dulaglutide) study * Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 26 weeks | Least squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 26 Weeks for Body Weight | Baseline, 26 weeks | Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks for Body Weight | Baseline, 52 weeks | Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate. |
| Change From Baseline to 26 Weeks on Body Mass Index (BMI) | Baseline, 26 weeks | Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks on Body Mass Index (BMI) | Baseline, 52 weeks | Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Baseline, 26 weeks | The 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; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least squares (LS) means of the mean of the 8 time points (daily mean) were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | Baseline, 52 weeks | The 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; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least squares (LS) means of the mean of the 8 time points (daily mean) were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate. |
| Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks | Baseline, 26 weeks | The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model. |
| Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 52 Weeks | Baseline, 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 logistic regression model with baseline, country, and treatment as factors included in the model. |
| Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | Baseline, 26 weeks | The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as percentages of a normal reference population (normal young adults). The normal reference populations were set at 100%. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | Baseline, 52 weeks | The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as percentages of a normal reference population (normal young adults). The normal reference populations were set at 100%. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26 Weeks in the EuroQol 5 | Baseline, 26 weeks | The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline. |
| Change From Baseline to 52 Weeks in the EuroQol 5 | Baseline, 52 weeks | The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline. |
| Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version | Baseline, 26 weeks | The Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) is used to assess participant treatment satisfaction at each study visit. The questionnaire consists of 8 items, 6 of which (1, and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied). The DTSQ change version (DTSQc) was not collected at 26 weeks. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate. |
| Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions | Baseline, 52 weeks | The Diabetes Treatment Satisfaction Questionnaire status (DTSQs) and change (DTSQc) versions are used to assess participant treatment satisfaction at each study visit and relative change in satisfaction from baseline, respectively. Both questionnaires consist of 8 items, 6 of which (1, and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The change version has the same 8 items as the status version with a small alteration of the wording of Item 7. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied) for the DTSQs and from -18 (much less satisfied) to +18 (much more satisfied) for the DTSQc. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate. |
| Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living | Baseline, 26 weeks | The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living \[APPADL\]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks in the Impact of Weight on Activities of Daily Living | Baseline, 52 weeks | The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living \[APPADL\]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception | Baseline, 26 weeks | The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks on the Impact of Weight on Self-Perception | Baseline, 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 and treatment as fixed effects and baseline as a covariate. |
| Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Baseline through 52 weeks | Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event since the previous inquiry. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 52 weeks. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module. |
| Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | Baseline, 26 weeks | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | Baseline, 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change in Baseline to 26 Weeks on Pulse Rate | Baseline, 26 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change in Baseline to 52 Weeks on Pulse Rate | Baseline, 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 26 Weeks on Blood Pressure | Baseline, 26 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline to 52 Weeks on Blood Pressure | Baseline, 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Number of Participants With Adjudicated Pancreatitis at 26 Weeks | Baseline through 26 weeks | The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 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 Pancreatitis at 52 Weeks | Baseline through 52 weeks | The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only participants with confirmed pancreatitis during treatment with LY2189265 (26 weeks through 52 weeks). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to 26 Weeks on Pancreatic Enzymes | Baseline, 26 weeks | Amylase (total and pancreas-derived) and lipase concentrations were measured. |
| Change From Baseline to 52 Weeks on Pancreatic Enzymes | Baseline, 52 weeks | Amylase (total and pancreas-derived) and lipase concentrations were measured. |
| Change From Baseline to 26 Weeks on Serum Calcitonin | Baseline, 26 weeks | — |
| Change From Baseline to 52 Weeks on Serum Calcitonin | Baseline, 52 weeks | — |
| Number of Self-reported Hypoglycemic Events at 26 Weeks | Baseline through 26 weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Self-reported Hypoglycemic Events at 52 Weeks | Baseline through 52 weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 52 weeks. 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 at 26 Weeks | Baseline through 26 weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of equal to or less than 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of equal to or less than 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 26 weeks. 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 at 52 Weeks | Baseline through 52 weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of equal to or less than millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of equal to or less than 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 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 Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks | Baseline through 26 weeks | Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. Time to start first new glucose-lowering intervention due to hyperglycemia (rescue therapy) was analyzed between the groups using the semi-parametric proportional hazard regression model with treatment group and country as fixed effects and baseline glycosylated hemoglobin (HbA1c) as a covariate. |
| Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks | Baseline through 52 weeks | Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. Time to start first new glucose-lowering intervention due to hyperglycemia (rescue therapy) was analyzed between the groups using the semi-parametric proportional hazard regression model with treatment group and country as fixed effects and baseline glycosylated hemoglobin (HbA1c) as a covariate. |
| Number of Participants With LY2189265 Antibodies at 26 Weeks | Baseline through 26 weeks | LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed. The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA were summarized. |
| Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug | 26 weeks through 52 weeks and 53 weeks through 4 weeks after last dose | LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed. The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA were summarized. |
| Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | Baseline through 26 weeks | A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 52 weeks | Least squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate. |
| Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values | Baseline, 26 weeks | — |
| Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values | Baseline, 52 weeks | — |
| Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP) | Baseline, 26 weeks | — |
| Pharmacokinetics: Area Under the Concentration Curve (AUC) for LY2189265 | 4 weeks, 13 weeks, 26 weeks, and 52 weeks | Evaluable pharmacokinetic concentrations from the 4-week, 13-week, 26-week, and 52-week timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state. |
| Number of Participants With Treatment Emergent Adverse Events at 52 Weeks | Baseline through 52 weeks | A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only TEAEs that occurred during treatment with LY2189265 (26 weeks through 52 weeks). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Countries
Argentina, Mexico, Puerto Rico, United States
Participant flow
Pre-assignment details
Due to ethical considerations and to preserve the blinding of the study, participants randomized to placebo at baseline were reassigned at 26 weeks to either 1.5 mg LY2189265 or 0.75 mg LY2189265 from 26 weeks through 52 weeks.
Participants by arm
| Arm | Count |
|---|---|
| 1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks | 279 |
| 0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks | 280 |
| Exenatide Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks | 276 |
| Placebo Placebo: subcutaneous (SC), once weekly for 26 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 26 weeks
Pioglitazone: at least 30 mg/day, oral, for 26 weeks | 141 |
| Total | 976 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 4 | 10 | 3 |
| Overall Study | Death | 1 | 1 | 0 | 0 |
| Overall Study | Entry Criteria Not Met | 3 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 2 | 3 |
| Overall Study | Lost to Follow-up | 7 | 10 | 13 | 5 |
| Overall Study | Physician Decision | 2 | 2 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 1 |
| Overall Study | Sponsor Decision | 0 | 0 | 3 | 0 |
| Overall Study | Treatment Noncompliance | 1 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 7 | 12 | 5 |
Baseline characteristics
| Characteristic | 1.5 mg LY2189265 | 0.75 mg LY2189265 | Exenatide | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 56.25 years STANDARD_DEVIATION 9.72 | 55.79 years STANDARD_DEVIATION 9.45 | 55.45 years STANDARD_DEVIATION 10.15 | 54.56 years STANDARD_DEVIATION 10.01 | 55.65 years STANDARD_DEVIATION 9.81 |
| Body Mass Index (BMI) | 33.09 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.33 | 33.00 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.5 | 33.54 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.36 | 32.90 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.66 | 33.16 kilograms per meter squared (kg/m^2) STANDARD_DEVIATION 5.43 |
| Body Weight | 96.22 kilograms STANDARD_DEVIATION 19.63 | 95.53 kilograms STANDARD_DEVIATION 20.56 | 97.37 kilograms STANDARD_DEVIATION 18.87 | 94.12 kilograms STANDARD_DEVIATION 19.28 | 96.04 kilograms STANDARD_DEVIATION 19.64 |
| Duration of Diabetes | 8.76 years STANDARD_DEVIATION 5.59 | 8.78 years STANDARD_DEVIATION 5.47 | 8.84 years STANDARD_DEVIATION 5.71 | 8.60 years STANDARD_DEVIATION 5.78 | 8.76 years STANDARD_DEVIATION 5.61 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 93 Participants | 102 Participants | 91 Participants | 45 Participants | 331 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants | 178 Participants | 184 Participants | 96 Participants | 644 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Fasting Serum Glucose | 9.00 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.09 | 8.84 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.76 | 9.11 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.04 | 9.22 millimoles per liter (mmol/L) STANDARD_DEVIATION 3.01 | 9.02 millimoles per liter (mmol/L) STANDARD_DEVIATION 2.97 |
| Glycosylated Hemoglobin (HbA1c) | 8.10 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.34 | 8.05 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.24 | 8.07 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.34 | 8.06 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.31 | 8.07 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.31 |
| Race (NIH/OMB) American Indian or Alaska Native | 40 Participants | 37 Participants | 38 Participants | 20 Participants | 135 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 8 Participants | 4 Participants | 6 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 24 Participants | 18 Participants | 10 Participants | 76 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 205 Participants | 207 Participants | 211 Participants | 103 Participants | 726 Participants |
| Region of Enrollment Argentina | 16 participants | 18 participants | 18 participants | 9 participants | 61 participants |
| Region of Enrollment Mexico | 37 participants | 36 participants | 35 participants | 19 participants | 127 participants |
| Region of Enrollment United States | 226 participants | 226 participants | 223 participants | 113 participants | 788 participants |
| Sex: Female, Male Female | 116 Participants | 112 Participants | 120 Participants | 58 Participants | 406 Participants |
| Sex: Female, Male Male | 163 Participants | 168 Participants | 156 Participants | 83 Participants | 570 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 194 / 280 | 215 / 279 | 196 / 278 | 103 / 141 | 218 / 280 | 228 / 279 | 223 / 278 | 47 / 62 | 55 / 62 |
| serious Total, serious adverse events | 15 / 280 | 12 / 279 | 15 / 278 | 12 / 141 | 22 / 280 | 18 / 279 | 27 / 278 | 6 / 62 | 9 / 62 |
Outcome results
Primary
Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
Least squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.51 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.30 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| Exenatide | Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.99 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| Placebo | Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.46 percentage of glycosylated hemoglobin | Standard Error 0.08 |
Comparison: Superiority analysis.p-value: <0.00195% CI: [-1.22, -0.88]ANCOVA
Comparison: Non-inferiority analysis.p-value: <0.000195% CI: [-0.66, -0.39]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-1.01, -0.67]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.66, -0.39]ANCOVA
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.44, -0.18]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.44, -0.18]ANCOVA
Secondary
Change From Baseline to 26 Weeks for Body Weight
Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable body weight data. Only pre-rescue measurements were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks for Body Weight | -1.34 kilograms (kg) | Standard Error 0.25 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks for Body Weight | 0.18 kilograms (kg) | Standard Error 0.25 |
| Exenatide | Change From Baseline to 26 Weeks for Body Weight | -1.14 kilograms (kg) | Standard Error 0.26 |
| Placebo | Change From Baseline to 26 Weeks for Body Weight | 1.37 kilograms (kg) | Standard Error 0.37 |
p-value: <0.00195% CI: [-3.58, -1.85]Mixed Models Analysis
p-value: 0.57195% CI: [-0.88, 0.49]Mixed Models Analysis
p-value: 0.00795% CI: [-2.06, -0.33]Mixed Models Analysis
p-value: <0.00195% CI: [0.64, 2.01]Mixed Models Analysis
p-value: <0.00195% CI: [-3.39, -1.65]Mixed Models Analysis
Secondary
Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles
The 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; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least squares (LS) means of the mean of the 8 time points (daily mean) were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable SMPG data. Only pre-rescue measurements were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | -46.82 milligrams per deciliter (mg/dL) | Standard Error 1.81 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | -42.09 milligrams per deciliter (mg/dL) | Standard Error 1.87 |
| Exenatide | Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | -37.48 milligrams per deciliter (mg/dL) | Standard Error 1.83 |
| Placebo | Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | -18.07 milligrams per deciliter (mg/dL) | Standard Error 2.68 |
p-value: <0.00195% CI: [-34.5, -23.02]Mixed Models Analysis
p-value: <0.00195% CI: [-13.62, -5.06]Mixed Models Analysis
p-value: <0.00195% CI: [-29.8, -18.24]Mixed Models Analysis
p-value: 0.03895% CI: [-8.95, -0.27]Mixed Models Analysis
p-value: <0.00195% CI: [-25.18, -13.65]Mixed Models Analysis
Secondary
Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values | NA |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values | NA |
| Exenatide | Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values | NA |
| Placebo | Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values | NA |
Secondary
Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP)
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable NT-proBNP 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 | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP) | -6.77 picograms per milliliter (pg/mL) | Inter-Quartile Range 91.13 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP) | -2.96 picograms per milliliter (pg/mL) | Inter-Quartile Range 189.94 |
| Exenatide | Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP) | -3.38 picograms per milliliter (pg/mL) | Inter-Quartile Range 208.92 |
| Placebo | Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP) | -0.85 picograms per milliliter (pg/mL) | Inter-Quartile Range 133.04 |
Secondary
Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version
The Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) is used to assess participant treatment satisfaction at each study visit. The questionnaire consists of 8 items, 6 of which (1, and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied). The DTSQ change version (DTSQc) was not collected at 26 weeks. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable DTSQs data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) used to impute missing postbaseline values. If there were no data after randomization, endpoint was considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version | 2.40 units on a scale | Standard Error 0.34 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version | 2.56 units on a scale | Standard Error 0.33 |
| Exenatide | Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version | 0.85 units on a scale | Standard Error 0.33 |
| Placebo | Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version | 0.49 units on a scale | Standard Error 0.45 |
Secondary
Change From Baseline to 26 Weeks in the EuroQol 5
The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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 Weeks in the EuroQol 5 | VAS Health State Score (n=270, 267, 264, 119) | 4.50 units on a scale | Standard Error 0.85 |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks in the EuroQol 5 | EQ-5D UK (n=270, 266, 264, 119) | 0.01 units on a scale | Standard Error 0.01 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in the EuroQol 5 | EQ-5D UK (n=270, 266, 264, 119) | 0.01 units on a scale | Standard Error 0.01 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in the EuroQol 5 | VAS Health State Score (n=270, 267, 264, 119) | 2.41 units on a scale | Standard Error 0.85 |
| Exenatide | Change From Baseline to 26 Weeks in the EuroQol 5 | VAS Health State Score (n=270, 267, 264, 119) | 3.94 units on a scale | Standard Error 0.85 |
| Exenatide | Change From Baseline to 26 Weeks in the EuroQol 5 | EQ-5D UK (n=270, 266, 264, 119) | 0.00 units on a scale | Standard Error 0.01 |
| Placebo | Change From Baseline to 26 Weeks in the EuroQol 5 | VAS Health State Score (n=270, 267, 264, 119) | 0.71 units on a scale | Standard Error 1.15 |
| Placebo | Change From Baseline to 26 Weeks in the EuroQol 5 | EQ-5D UK (n=270, 266, 264, 119) | -0.00 units on a scale | Standard Error 0.02 |
Secondary
Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living
The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living \[APPADL\]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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 | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living | 0.18 units on a scale | Standard Error 0.27 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living | 0.12 units on a scale | Standard Error 0.27 |
| Exenatide | Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living | 0.47 units on a scale | Standard Error 0.27 |
| Placebo | Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living | 0.03 units on a scale | Standard Error 0.36 |
Secondary
Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S)
The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as percentages of a normal reference population (normal young adults). The normal reference populations were set at 100%. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable HOMA2-%B or HOMA2-%S data. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B | 36.14 percentage of HOMA2 | Standard Error 2.6 |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S | -3.14 percentage of HOMA2 | Standard Error 2.91 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S | 1.16 percentage of HOMA2 | Standard Error 2.97 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B | 23.61 percentage of HOMA2 | Standard Error 2.67 |
| Exenatide | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B | 15.02 percentage of HOMA2 | Standard Error 2.62 |
| Exenatide | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S | -1.59 percentage of HOMA2 | Standard Error 2.92 |
| Placebo | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B | 0.93 percentage of HOMA2 | Standard Error 3.66 |
| Placebo | Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S | 2.56 percentage of HOMA2 | Standard Error 4.07 |
p-value: <0.00195% CI: [27.26, 43.16]Mixed Models Analysis
p-value: <0.00195% CI: [14.97, 27.28]Mixed Models Analysis
p-value: <0.00195% CI: [14.63, 30.72]Mixed Models Analysis
p-value: 0.00795% CI: [2.31, 14.87]Mixed Models Analysis
p-value: <0.00195% CI: [6.06, 22.11]Mixed Models Analysis
p-value: 0.20795% CI: [-14.56, 3.17]Mixed Models Analysis
p-value: 0.65995% CI: [-8.41, 5.32]Mixed Models Analysis
p-value: 0.75995% CI: [-10.37, 7.56]Mixed Models Analysis
p-value: 0.44195% CI: [-4.25, 9.76]Mixed Models Analysis
p-value: 0.36295% CI: [-13.1, 4.79]Mixed Models Analysis
Secondary
Change From Baseline to 26 Weeks on 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least one dose of LY2189265, Exenatide, or Placebo with evaluable blood pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Blood Pressure | Seated SBP (n=263, 266, 259, 127) | 0.11 millimeters of mercury (mmHg) | Standard Error 0.83 |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Blood Pressure | Seated DBP (n=263, 266, 259, 127) | 0.76 millimeters of mercury (mmHg) | Standard Error 0.55 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Blood Pressure | Seated DBP (n=263, 266, 259, 127) | 0.56 millimeters of mercury (mmHg) | Standard Error 0.54 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Blood Pressure | Seated SBP (n=263, 266, 259, 127) | -0.36 millimeters of mercury (mmHg) | Standard Error 0.82 |
| Exenatide | Change From Baseline to 26 Weeks on Blood Pressure | Seated SBP (n=263, 266, 259, 127) | 0.06 millimeters of mercury (mmHg) | Standard Error 0.83 |
| Exenatide | Change From Baseline to 26 Weeks on Blood Pressure | Seated DBP (n=263, 266, 259, 127) | -0.11 millimeters of mercury (mmHg) | Standard Error 0.55 |
| Placebo | Change From Baseline to 26 Weeks on Blood Pressure | Seated SBP (n=263, 266, 259, 127) | 3.40 millimeters of mercury (mmHg) | Standard Error 1.13 |
| Placebo | Change From Baseline to 26 Weeks on Blood Pressure | Seated DBP (n=263, 266, 259, 127) | 1.25 millimeters of mercury (mmHg) | Standard Error 0.75 |
Secondary
Change From Baseline to 26 Weeks on Body Mass Index (BMI)
Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable BMI data. Only pre-rescue measurements were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Body Mass Index (BMI) | -0.48 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Body Mass Index (BMI) | 0.07 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| Exenatide | Change From Baseline to 26 Weeks on Body Mass Index (BMI) | -0.41 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| Placebo | Change From Baseline to 26 Weeks on Body Mass Index (BMI) | 0.49 kilograms per meter squared (kg/m^2) | Standard Error 0.13 |
p-value: <0.00195% CI: [-1.27, -0.67]Mixed Models Analysis
p-value: 0.56895% CI: [-0.31, 0.17]Mixed Models Analysis
p-value: 0.00695% CI: [-0.72, -0.12]Mixed Models Analysis
p-value: <0.00195% CI: [0.24, 0.71]Mixed Models Analysis
p-value: <0.00195% CI: [-1.2, -0.6]Mixed Models Analysis
Secondary
Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable ECG QTcF Interval or PR interval data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval (n=253, 260, 250, 120) | -1.11 milliseconds (msec) | Standard Error 1 |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval (n=252, 259, 246, 116) | 2.35 milliseconds (msec) | Standard Error 0.89 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval (n=252, 259, 246, 116) | 0.93 milliseconds (msec) | Standard Error 0.88 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval (n=253, 260, 250, 120) | 0.91 milliseconds (msec) | Standard Error 0.99 |
| Exenatide | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval (n=253, 260, 250, 120) | 1.21 milliseconds (msec) | Standard Error 1 |
| Exenatide | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval (n=252, 259, 246, 116) | 1.01 milliseconds (msec) | Standard Error 0.89 |
| Placebo | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval (n=253, 260, 250, 120) | 1.32 milliseconds (msec) | Standard Error 1.33 |
| Placebo | Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval (n=252, 259, 246, 116) | -1.83 milliseconds (msec) | Standard Error 1.2 |
Secondary
Change From Baseline to 26 Weeks on Pancreatic Enzymes
Amylase (total and pancreas-derived) and lipase concentrations were measured.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Total (n=253, 253, 254, 127) | 12.50 units per liter | Inter-Quartile Range 26.55 |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Lipase (n=198, 203, 222, 114) | 10.34 units per liter | — |
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived (n=237, 247, 246, 122) | 14.81 units per liter | — |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Total (n=253, 253, 254, 127) | 3.28 units per liter | Inter-Quartile Range 24.24 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Lipase (n=198, 203, 222, 114) | 0.00 units per liter | — |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived (n=237, 247, 246, 122) | 10.34 units per liter | — |
| Exenatide | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived (n=237, 247, 246, 122) | 5.56 units per liter | — |
| Exenatide | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Total (n=253, 253, 254, 127) | 5.56 units per liter | Inter-Quartile Range 26.61 |
| Exenatide | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Lipase (n=198, 203, 222, 114) | 3.94 units per liter | — |
| Placebo | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Total (n=253, 253, 254, 127) | -3.33 units per liter | Inter-Quartile Range 27.51 |
| Placebo | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Lipase (n=198, 203, 222, 114) | -9.53 units per liter | — |
| Placebo | Change From Baseline to 26 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived (n=237, 247, 246, 122) | -3.77 units per liter | — |
Secondary
Change From Baseline to 26 Weeks on Serum Calcitonin
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on Serum Calcitonin | 0.20 picograms per milliliter (pg/mL) | Standard Deviation 1.2 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on Serum Calcitonin | 0.22 picograms per milliliter (pg/mL) | Standard Deviation 1.91 |
| Exenatide | Change From Baseline to 26 Weeks on Serum Calcitonin | 0.05 picograms per milliliter (pg/mL) | Standard Deviation 1.48 |
| Placebo | Change From Baseline to 26 Weeks on Serum Calcitonin | 0.05 picograms per milliliter (pg/mL) | Standard Deviation 0.89 |
Secondary
Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception
The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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 | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception | 0.56 units on a scale | Standard Error 0.15 |
| 0.75 mg LY2189265 | Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception | 0.47 units on a scale | Standard Error 0.15 |
| Exenatide | Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception | 0.46 units on a scale | Standard Error 0.15 |
| Placebo | Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception | 0.45 units on a scale | Standard Error 0.2 |
Secondary
Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
Least squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable HbA1c data. Only pre-rescue measurements were used. 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 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.36 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -1.07 percentage of glycosylated hemoglobin | Standard Error 0.08 |
| Exenatide | Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.80 percentage of glycosylated hemoglobin | Standard Error 0.08 |
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.73, -0.39]ANCOVA
Comparison: Non-inferiority analysis.p-value: <0.00195% CI: [-0.44, -0.11]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.73, -0.39]ANCOVA
Comparison: Superiority analysis.p-value: <0.00195% CI: [-0.44, -0.11]ANCOVA
Secondary
Change From Baseline to 52 Weeks for Body Weight
Least squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable body weight data. Only pre-rescue measurements were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks for Body Weight | -1.08 kilograms (kg) | Standard Error 0.34 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks for Body Weight | 0.49 kilograms (kg) | Standard Error 0.34 |
| Exenatide | Change From Baseline to 52 Weeks for Body Weight | -0.76 kilograms (kg) | Standard Error 0.35 |
p-value: 0.50795% CI: [-1.25, 0.62]Mixed Models Analysis
p-value: 0.00995% CI: [0.32, 2.19]Mixed Models Analysis
Secondary
Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles
The 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; 2 hours post-evening meal; bedtime; and 3AM or 5 hours after bedtime. Least squares (LS) means of the mean of the 8 time points (daily mean) were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, country, visit, and treatment-by-visit as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable SMPG data. Only pre-rescue measurements were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | -43.84 milligrams per deciliter (mg/dL) | Standard Error 2.07 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | -40.62 milligrams per deciliter (mg/dL) | Standard Error 2.12 |
| Exenatide | Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles | -36.16 milligrams per deciliter (mg/dL) | Standard Error 2.11 |
p-value: 0.00495% CI: [-12.84, -2.52]Mixed Models Analysis
p-value: 0.09295% CI: [-9.66, 0.73]Mixed Models Analysis
Secondary
Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values | NA |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values | NA |
| Exenatide | Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values | NA |
Secondary
Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions
The Diabetes Treatment Satisfaction Questionnaire status (DTSQs) and change (DTSQc) versions are used to assess participant treatment satisfaction at each study visit and relative change in satisfaction from baseline, respectively. Both questionnaires consist of 8 items, 6 of which (1, and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The change version has the same 8 items as the status version with a small alteration of the wording of Item 7. Scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from 0 (very dissatisfied) to 36 (very satisfied) for the DTSQs and from -18 (much less satisfied) to +18 (much more satisfied) for the DTSQc. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline score as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable DTSQs or DTSQc data. Only pre-rescue measurements were used. 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 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions | DTSQs Treatment Satisfaction (n=270, 268, 266) | 2.05 units on a scale | Standard Error 0.36 |
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions | DTSQc Treatment Satisfaction (n=249, 237, 226) | 15.36 units on a scale | Standard Error 0.4 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions | DTSQs Treatment Satisfaction (n=270, 268, 266) | 2.11 units on a scale | Standard Error 0.36 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions | DTSQc Treatment Satisfaction (n=249, 237, 226) | 15.46 units on a scale | Standard Error 0.41 |
| Exenatide | Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions | DTSQs Treatment Satisfaction (n=270, 268, 266) | 0.69 units on a scale | Standard Error 0.36 |
| Exenatide | Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions | DTSQc Treatment Satisfaction (n=249, 237, 226) | 14.01 units on a scale | Standard Error 0.41 |
Secondary
Change From Baseline to 52 Weeks in the EuroQol 5
The European Quality of Life - 5 dimensions (EQ-5D) questionnaire is a generic, multidimensional, health-related, quality-of-life instrument. It consists of 2 parts: the first part assesses 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that have 3 possible levels of response (no problem, some problem, or extreme problem). These dimensions are converted into a weighted health-state Index Score. The EQ-5D United Kingdom (UK) score ranges from -0.59 to 1.0, where a score of 1.0 indicates perfect health and negative values are valued as worse than dead. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participants rated their perceived health state on that day from 0 (worst imaginable health state) to 100 (best imaginable health). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) and adjusted by treatment, country, and baseline.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable EQ-5D data. Only pre-rescue measurements were used. 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 52 Weeks in the EuroQol 5 | VAS Health State Score (n=270, 267, 264) | 5.15 units on a scale | Standard Error 0.89 |
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks in the EuroQol 5 | EQ-5D UK (n=270, 266, 264) | 0.02 units on a scale | Standard Error 0.01 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in the EuroQol 5 | VAS Health State Score (n=270, 267, 264) | 3.52 units on a scale | Standard Error 0.89 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in the EuroQol 5 | EQ-5D UK (n=270, 266, 264) | 0.01 units on a scale | Standard Error 0.01 |
| Exenatide | Change From Baseline to 52 Weeks in the EuroQol 5 | VAS Health State Score (n=270, 267, 264) | 3.51 units on a scale | Standard Error 0.89 |
| Exenatide | Change From Baseline to 52 Weeks in the EuroQol 5 | EQ-5D UK (n=270, 266, 264) | -0.00 units on a scale | Standard Error 0.01 |
Secondary
Change From Baseline to 52 Weeks in the Impact of Weight on Activities of Daily Living
The Impact of Weight on Activities of Daily Living (renamed the Ability to Perform Physical Activities of Daily Living \[APPADL\]) questionnaire contains 7 items that assess how difficult it is for participants to engage in certain activities considered to be integral to normal daily life, such as walking, standing and climbing stairs. Items are scored on a 5-point numeric rating scale where 5 = not at all difficult and 1 = unable to do. The individual scores from all 7 items are summed and a single total score is calculated and may range between 7 and 35. A higher score indicates better ability to perform activities of daily living. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable APPADL data. Only pre-rescue measurements were used. 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 Weeks in the Impact of Weight on Activities of Daily Living | 0.18 units on a scale | Standard Error 0.29 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in the Impact of Weight on Activities of Daily Living | -0.18 units on a scale | Standard Error 0.29 |
| Exenatide | Change From Baseline to 52 Weeks in the Impact of Weight on Activities of Daily Living | 0.35 units on a scale | Standard Error 0.29 |
Secondary
Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S)
The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as percentages of a normal reference population (normal young adults). The normal reference populations were set at 100%. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable HOMA2-%B or HOMA2-%S data. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B | 35.21 percentage of HOMA2 | Standard Error 2.63 |
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S | -7.48 percentage of HOMA2 | Standard Error 2.93 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B | 25.69 percentage of HOMA2 | Standard Error 2.7 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S | -5.49 percentage of HOMA2 | Standard Error 3.01 |
| Exenatide | Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%B | 13.57 percentage of HOMA2 | Standard Error 2.75 |
| Exenatide | Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S) | HOMA2-%S | -3.75 percentage of HOMA2 | Standard Error 3.07 |
p-value: <0.00195% CI: [15.2, 28.08]Mixed Models Analysis
p-value: <0.00195% CI: [5.56, 18.68]Mixed Models Analysis
p-value: 0.30795% CI: [-10.9, 3.43]Mixed Models Analysis
p-value: 0.63895% CI: [-9.05, 5.55]Mixed Models Analysis
Secondary
Change From Baseline to 52 Weeks on 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable blood pressure data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Blood Pressure | Seated SBP (n=248, 256, 238) | 0.83 millimeters of mercury (mmHg) | Standard Error 0.87 |
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Blood Pressure | Seated DBP (n=248, 256, 238) | 0.89 millimeters of mercury (mmHg) | Standard Error 0.57 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Blood Pressure | Seated SBP (n=248, 256, 238) | 1.62 millimeters of mercury (mmHg) | Standard Error 0.85 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Blood Pressure | Seated DBP (n=248, 256, 238) | 0.76 millimeters of mercury (mmHg) | Standard Error 0.57 |
| Exenatide | Change From Baseline to 52 Weeks on Blood Pressure | Seated SBP (n=248, 256, 238) | 0.02 millimeters of mercury (mmHg) | Standard Error 0.88 |
| Exenatide | Change From Baseline to 52 Weeks on Blood Pressure | Seated DBP (n=248, 256, 238) | 0.02 millimeters of mercury (mmHg) | Standard Error 0.58 |
Secondary
Change From Baseline to 52 Weeks on Body Mass Index (BMI)
Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable BMI data. Only pre-rescue measurements were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Body Mass Index (BMI) | -0.37 kilograms per meter squared (kg/m^2) | Standard Error 0.12 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Body Mass Index (BMI) | 0.18 kilograms per meter squared (kg/m^2) | Standard Error 0.12 |
| Exenatide | Change From Baseline to 52 Weeks on Body Mass Index (BMI) | -0.28 kilograms per meter squared (kg/m^2) | Standard Error 0.12 |
p-value: 0.5895% CI: [-0.42, 0.23]Mixed Models Analysis
p-value: 0.00595% CI: [0.14, 0.79]Mixed Models Analysis
Secondary
Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable ECG QTcF Interval or PR Interval data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval (n=239, 243, 226) | 1.28 milliseconds (msec) | Standard Error 1.07 |
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval (n=237, 243, 220) | 2.57 milliseconds (msec) | Standard Error 0.96 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval (n=239, 243, 226) | 2.30 milliseconds (msec) | Standard Error 1.07 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval (n=237, 243, 220) | 0.69 milliseconds (msec) | Standard Error 0.96 |
| Exenatide | Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval (n=239, 243, 226) | 2.52 milliseconds (msec) | Standard Error 1.1 |
| Exenatide | Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval (n=237, 243, 220) | -0.82 milliseconds (msec) | Standard Error 0.99 |
Secondary
Change From Baseline to 52 Weeks on Pancreatic Enzymes
Amylase (total and pancreas-derived) and lipase concentrations were measured.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug 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 52 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived (n=236, 253, 246) | 16.67 units per liter |
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Amylase, Total (n=255, 263, 261) | 9.21 units per liter |
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Lipase (n=201, 205, 221) | 5.45 units per liter |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived (n=236, 253, 246) | 7.69 units per liter |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Amylase, Total (n=255, 263, 261) | 2.78 units per liter |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Lipase (n=201, 205, 221) | 0.00 units per liter |
| Exenatide | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Amylase, Total (n=255, 263, 261) | 2.38 units per liter |
| Exenatide | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Lipase (n=201, 205, 221) | 3.57 units per liter |
| Exenatide | Change From Baseline to 52 Weeks on Pancreatic Enzymes | Amylase, Pancreas-derived (n=236, 253, 246) | 7.85 units per liter |
Secondary
Change From Baseline to 52 Weeks on Serum Calcitonin
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug 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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52 Weeks on Serum Calcitonin | 0.21 picograms per milliliter (pg/mL) | Standard Deviation 1.29 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on Serum Calcitonin | 0.05 picograms per milliliter (pg/mL) | Standard Deviation 1.79 |
| Exenatide | Change From Baseline to 52 Weeks on Serum Calcitonin | 0.10 picograms per milliliter (pg/mL) | Standard Deviation 1.67 |
Secondary
Change From Baseline to 52 Weeks on the Impact of Weight on Self-Perception
The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable IW-SP data. Only pre-rescue measurements were used. 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 Weeks on the Impact of Weight on Self-Perception | 0.50 units on a scale | Standard Error 0.15 |
| 0.75 mg LY2189265 | Change From Baseline to 52 Weeks on the Impact of Weight on Self-Perception | 0.47 units on a scale | Standard Error 0.15 |
| Exenatide | Change From Baseline to 52 Weeks on the Impact of Weight on Self-Perception | 0.64 units on a scale | Standard Error 0.15 |
Secondary
Change in Baseline to 26 Weeks on 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo with evaluable seated pulse rate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change in Baseline to 26 Weeks on Pulse Rate | 2.80 beats per minute (bpm) | Standard Error 0.52 |
| 0.75 mg LY2189265 | Change in Baseline to 26 Weeks on Pulse Rate | 2.80 beats per minute (bpm) | Standard Error 0.51 |
| Exenatide | Change in Baseline to 26 Weeks on Pulse Rate | 1.18 beats per minute (bpm) | Standard Error 0.52 |
| Placebo | Change in Baseline to 26 Weeks on Pulse Rate | 0.61 beats per minute (bpm) | Standard Error 0.7 |
Secondary
Change in Baseline to 52 Weeks on 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, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable seated pulse rate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change in Baseline to 52 Weeks on Pulse Rate | 1.68 beats per minute (bpm) | Standard Error 0.56 |
| 0.75 mg LY2189265 | Change in Baseline to 52 Weeks on Pulse Rate | 1.56 beats per minute (bpm) | Standard Error 0.55 |
| Exenatide | Change in Baseline to 52 Weeks on Pulse Rate | 1.15 beats per minute (bpm) | Standard Error 0.56 |
Secondary
Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks
Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. Time to start first new glucose-lowering intervention due to hyperglycemia (rescue therapy) was analyzed between the groups using the semi-parametric proportional hazard regression model with treatment group and country as fixed effects and baseline glycosylated hemoglobin (HbA1c) as a covariate.
Time frame: Baseline through 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks | 4 participants |
| 0.75 mg LY2189265 | Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks | 14 participants |
| Exenatide | Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks | 13 participants |
| Placebo | Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks | 22 participants |
Secondary
Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks
Rescue therapy was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. Time to start first new glucose-lowering intervention due to hyperglycemia (rescue therapy) was analyzed between the groups using the semi-parametric proportional hazard regression model with treatment group and country as fixed effects and baseline glycosylated hemoglobin (HbA1c) as a covariate.
Time frame: Baseline through 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks | 10 participants |
| 0.75 mg LY2189265 | Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks | 27 participants |
| Exenatide | Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks | 31 participants |
Secondary
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks
Information on cardiovascular (CV) risk factors was collected at baseline. Data on any new CV event was prospectively collected using a CV event electronic case report form. At prespecified visits, participants were asked about any new CV event since the previous inquiry. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 52 weeks. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.
Time frame: Baseline through 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug. The number of participants with adjudicated CV events was not collected at 26 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any Fatal Event | 1 participants |
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any CV Event | 3 participants |
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any Non-fatal CV Event | 3 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any Fatal Event | 0 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any CV Event | 2 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any Non-fatal CV Event | 2 participants |
| Exenatide | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any CV Event | 2 participants |
| Exenatide | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any Non-fatal CV Event | 2 participants |
| Exenatide | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks | Any Fatal Event | 0 participants |
Secondary
Number of Participants With Adjudicated Pancreatitis at 26 Weeks
The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Pancreatitis at 26 Weeks | 0 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Pancreatitis at 26 Weeks | 0 participants |
| Exenatide | Number of Participants With Adjudicated Pancreatitis at 26 Weeks | 0 participants |
| Placebo | Number of Participants With Adjudicated Pancreatitis at 26 Weeks | 0 participants |
Secondary
Number of Participants With Adjudicated Pancreatitis at 52 Weeks
The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only participants with confirmed pancreatitis during treatment with LY2189265 (26 weeks through 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 at baseline to LY2189265, Exenatide, or Placebo and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Pancreatitis at 52 Weeks | 1 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Pancreatitis at 52 Weeks | 0 participants |
| Exenatide | Number of Participants With Adjudicated Pancreatitis at 52 Weeks | 0 participants |
| Placebo | Number of Participants With Adjudicated Pancreatitis at 52 Weeks | 0 participants |
| Placebo/0.75 mg LY2189265 | Number of Participants With Adjudicated Pancreatitis at 52 Weeks | 0 participants |
Secondary
Number of Participants With LY2189265 Antibodies at 26 Weeks
LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed. The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA were summarized.
Time frame: Baseline through 26 weeks
Population: Participants who were randomized and received at least one dose of LY2189265, Exenatide, or Placebo with evaluable LY2189265 ADA data. In the clinically evaluated dose range of LY2189265, no dose effect on the magnitude of the anti-LY2189265 immune response was observed. Therefore, results were combined for the 0.75 mg and 1.5 mg LY2189265 groups.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With LY2189265 Antibodies at 26 Weeks | 6 participants |
| 0.75 mg LY2189265 | Number of Participants With LY2189265 Antibodies at 26 Weeks | 12 participants |
| Exenatide | Number of Participants With LY2189265 Antibodies at 26 Weeks | 2 participants |
Secondary
Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug
LY2189265 (Dulaglutide) anti-drug antibodies (ADA) were assessed. The number of participants with initial postbaseline detection of treatment emergent (defined as a 4-fold increase in the ADA titer from baseline) LY2189265 ADA were summarized.
Time frame: 26 weeks through 52 weeks and 53 weeks through 4 weeks after last dose
Population: Participants who were randomized and received at least one dose of LY2189265, Exenatide, or Placebo with evaluable LY2189265 ADA data. In the clinically evaluated dose range of LY2189265, no dose effect on the magnitude of the anti-LY2189265 immune response was observed. Therefore, results were combined for the 0.75 mg and 1.5 mg LY2189265 groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug | 52 weeks | 3 participants |
| 1.5 mg LY2189265 | Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug | 4 weeks after last study dose | 1 participants |
| 0.75 mg LY2189265 | Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug | 52 weeks | 2 participants |
| 0.75 mg LY2189265 | Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug | 4 weeks after last study dose | 0 participants |
| Exenatide | Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug | 52 weeks | 2 participants |
| Exenatide | Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug | 4 weeks after last study dose | 1 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events at 26 Weeks
A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | 215 participants |
| 0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | 199 participants |
| Exenatide | Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | 198 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events at 26 Weeks | 104 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events at 52 Weeks
A treatment-emergent adverse event (TEAE) was defined as an event that first occurs or worsens (increases in severity) after baseline regardless of causality or severity. The number of participants with one or more TEAE is summarized cumulatively at 52 weeks, with the exception of the Placebo/1.5 mg LY2189265 and Placebo/0.75 mg LY2189265 treatment groups, which include only TEAEs that occurred during treatment with LY2189265 (26 weeks through 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 at baseline to LY2189265, Exenatide, or Placebo and received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 52 Weeks | 226 participants |
| 0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 52 Weeks | 220 participants |
| Exenatide | Number of Participants With Treatment Emergent Adverse Events at 52 Weeks | 221 participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events at 52 Weeks | 47 participants |
| Placebo/0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 52 Weeks | 41 participants |
Secondary
Number of Self-reported Hypoglycemic Events at 26 Weeks
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 9 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Documented Symptomatic HE | 31 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Probable Symptomatic HE | 5 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 26 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 0 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 95 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 15 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Probable Symptomatic HE | 16 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Documented Symptomatic HE | 25 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 0 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 51 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 1 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 26 Weeks | Documented Symptomatic HE | 146 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 31 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 26 Weeks | Probable Symptomatic HE | 3 events |
| Placebo | Number of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 6 events |
| Placebo | Number of Self-reported Hypoglycemic Events at 26 Weeks | Documented Symptomatic HE | 4 events |
| Placebo | Number of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 0 events |
| Placebo | Number of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 5 events |
| Placebo | Number of Self-reported Hypoglycemic Events at 26 Weeks | Probable Symptomatic HE | 3 events |
Secondary
Number of Self-reported Hypoglycemic Events at 52 Weeks
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of less than or equal to 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events is summarized cumulatively at 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 at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Nocturnal HE | 20 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic HE | 47 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Severe HE | 0 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Documented Symptomatic HE | 53 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Probable Symptomatic HE | 8 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Severe HE | 0 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Documented Symptomatic HE | 39 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic HE | 157 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Nocturnal HE | 29 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 52 Weeks | Probable Symptomatic HE | 22 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 52 Weeks | Probable Symptomatic HE | 4 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 52 Weeks | Nocturnal HE | 57 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 52 Weeks | Severe HE | 2 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic HE | 98 events |
| Exenatide | Number of Self-reported Hypoglycemic Events at 52 Weeks | Documented Symptomatic HE | 205 events |
Secondary
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks
The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, country, and treatment as factors included in the model.
Time frame: Baseline, 26 weeks
Population: Participants who were randomized and received at least 1 dose of LY2189265, Exenatide, or Placebo 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 26 Weeks | HbA1c Less Than 7% | 78.2 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 26 Weeks | HbA1c Less Than or Equal to 6.5% | 62.7 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 26 Weeks | HbA1c Less Than or Equal to 6.5% | 53.2 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 26 Weeks | HbA1c Less Than 7% | 65.8 percentage of participants |
| Exenatide | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks | HbA1c Less Than 7% | 52.3 percentage of participants |
| Exenatide | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks | HbA1c Less Than or Equal to 6.5% | 38.0 percentage of participants |
| Placebo | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks | HbA1c Less Than 7% | 42.9 percentage of participants |
| Placebo | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks | HbA1c Less Than or Equal to 6.5% | 24.4 percentage of participants |
p-value: <0.00195% CI: [2.9, 6.8]Regression, Logistic
p-value: <0.00195% CI: [7.4, 23.4]Regression, Logistic
p-value: <0.00195% CI: [3.9, 10.1]Regression, Logistic
p-value: <0.00195% CI: [2.8, 8]Regression, Logistic
p-value: <0.00195% CI: [1.5, 3.5]Regression, Logistic
p-value: 0.00495% CI: [1.3, 3.5]Regression, Logistic
p-value: <0.00195% CI: [6.7, 20.8]Regression, Logistic
p-value: <0.00195% CI: [3.7, 10.9]Regression, Logistic
p-value: <0.00195% CI: [1.6, 3.5]Regression, Logistic
p-value: <0.00195% CI: [1.6, 4.6]Regression, Logistic
Secondary
Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 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 logistic regression model with baseline, country, and treatment as factors included in the model.
Time frame: Baseline, 52 weeks
Population: Participants who were randomized at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug with evaluable HbA1c data. Only pre-rescue measurements were used. 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 52 Weeks | HbA1c Less Than 7.0% | 70.8 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 52 Weeks | HbA1c Less Than or Equal to 6.5% | 57.2 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 52 Weeks | HbA1c Less Than 7.0% | 59.1 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 52 Weeks | HbA1c Less Than or Equal to 6.5% | 48.3 percentage of participants |
| Exenatide | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 52 Weeks | HbA1c Less Than 7.0% | 49.2 percentage of participants |
| Exenatide | Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 52 Weeks | HbA1c Less Than or Equal to 6.5% | 34.6 percentage of participants |
p-value: <0.00195% CI: [2.4, 5.6]Regression, Logistic
p-value: 0.00895% CI: [1.1, 2.5]Regression, Logistic
p-value: <0.00195% CI: [2.3, 5.1]Regression, Logistic
p-value: <0.00195% CI: [1.4, 3.1]Regression, Logistic
Secondary
Pharmacokinetics: Area Under the Concentration Curve (AUC) for LY2189265
Evaluable pharmacokinetic concentrations from the 4-week, 13-week, 26-week, and 52-week timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.
Time frame: 4 weeks, 13 weeks, 26 weeks, and 52 weeks
Population: Participants who were randomized at baseline to LY2189265 and received at least 1 dose of study drug with evaluable AUC data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Pharmacokinetics: Area Under the Concentration Curve (AUC) for LY2189265 | 12383 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 5433 |
| 0.75 mg LY2189265 | Pharmacokinetics: Area Under the Concentration Curve (AUC) for LY2189265 | 6627 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 2487 |
Secondary
Rate of Self-reported Hypoglycemic Events at 26 Weeks
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of equal to or less than 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of equal to or less than 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks
Population: Participants who were randomized and received at least one dose of LY2189265, Exenatide, or Placebo. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 0.06 events per participant per year | Standard Deviation 0.6 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Documented symptomatic HE | 0.22 events per participant per year | Standard Deviation 1.94 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Probable symptomatic HE | 0.04 events per participant per year | Standard Deviation 0.37 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 0.19 events per participant per year | Standard Deviation 1.13 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 0.00 events per participant per year | Standard Deviation 0 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 0.69 events per participant per year | Standard Deviation 4.74 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 0.19 events per participant per year | Standard Deviation 1.74 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Probable symptomatic HE | 0.24 events per participant per year | Standard Deviation 2.44 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Documented symptomatic HE | 0.18 events per participant per year | Standard Deviation 0.97 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 0.00 events per participant per year | Standard Deviation 0 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 0.38 events per participant per year | Standard Deviation 1.74 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 0.01 events per participant per year | Standard Deviation 0.12 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Documented symptomatic HE | 1.07 events per participant per year | Standard Deviation 4.9 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 0.23 events per participant per year | Standard Deviation 1.16 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Probable symptomatic HE | 0.02 events per participant per year | Standard Deviation 0.21 |
| Placebo | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Nocturnal HE | 0.27 events per participant per year | Standard Deviation 2.51 |
| Placebo | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Documented symptomatic HE | 0.06 events per participant per year | Standard Deviation 0.48 |
| Placebo | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Severe HE | 0.00 events per participant per year | Standard Deviation 0 |
| Placebo | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Asymptomatic HE | 0.27 events per participant per year | Standard Deviation 2.44 |
| Placebo | Rate of Self-reported Hypoglycemic Events at 26 Weeks | Probable symptomatic HE | 0.04 events per participant per year | Standard Deviation 0.51 |
Secondary
Rate of Self-reported Hypoglycemic Events at 52 Weeks
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of equal to or less than millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of equal to or less than 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 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 at baseline to LY2189265 or Exenatide and received at least 1 dose of study drug. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Nocturnal HE | 0.07 events per participant per year | Standard Deviation 0.63 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic HE | 0.17 events per participant per year | Standard Deviation 1.05 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Severe HE | 0.00 events per participant per year | Standard Deviation 0 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Documented symptomatic HE | 0.19 events per participant per year | Standard Deviation 1.23 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Probable symptomatic HE | 0.03 events per participant per year | Standard Deviation 0.26 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic HE | 0.56 events per participant per year | Standard Deviation 3.57 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Severe HE | 0.00 events per participant per year | Standard Deviation 0 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Documented symptomatic HE | 0.14 events per participant per year | Standard Deviation 0.78 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Nocturnal HE | 0.19 events per participant per year | Standard Deviation 1.72 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Probable symptomatic HE | 0.21 events per participant per year | Standard Deviation 2.38 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Probable symptomatic HE | 0.02 events per participant per year | Standard Deviation 0.16 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Nocturnal HE | 0.21 events per participant per year | Standard Deviation 1.06 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Severe HE | 0.01 events per participant per year | Standard Deviation 0.09 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic HE | 0.37 events per participant per year | Standard Deviation 1.81 |
| Exenatide | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Documented symptomatic HE | 0.76 events per participant per year | Standard Deviation 3.18 |