Diabetes Mellitus, Type 2
Conditions
Brief summary
The purpose of this study is to determine if LY2189265 is safe and effective in reducing glycosylated hemoglobin (HbA1c) as compared to metformin in participants with Type 2 Diabetes.
Detailed description
The term rescue therapy in this trial was defined primarily as additional nontrial antidiabetic medication for the management of severe, persistent hyperglycemia or alternative antidiabetic medication following study drug discontinuation. For efficacy analyses, participants who received rescue medication were included in the analysis population, but only measurements obtained prior to taking rescue therapy were included in the efficacy analysis. For safety analyses, with the exception of hypoglycemia outcomes, all measurements including those obtained after taking rescue therapy were included in the analysis.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes for greater than or equal to 3 months and less than or equal to 5 years based on the disease diagnostic criteria (refer to the World Health Organization's \[WHO\] Classification of Diabetes). * Are treatment-naïve, not optimally controlled with diet and exercise alone, or are taking 1 oral antihyperglycemic medication (OAM) as monotherapy (excluding thiazolidinediones). For those on 1 OAM, the dose must be less than or equal to 50% the maximum authorized per local label. * Are able and willing to tolerate a minimum dose of 1500 milligrams per day (mg/day) or up to 2000 mg/day of metformin. * Have glycosylated hemoglobin (HbA1c) greater than or equal to 6.5% to less than or equal to 9.5%. * Females of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must: a) test negative for pregnancy at screening based on a serum pregnancy test, and b) agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or c) not be breastfeeding. * Have a stable weight (plus or minus 5%) greater than or equal to 3 months prior to screening. * Have a body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m\^2), inclusive. * Are well-motivated, capable, and willing to: a) perform self-monitored blood glucose (SMBG) testing; b) learn how to self-inject treatment (LY2189265 or placebo) and c) maintain a study diary.
Exclusion criteria
* Have type 1 diabetes mellitus. * Are being or have been treated with any of the following medications: a) chronically treated with insulin for the treatment of diabetes in the past; however, a short-term use of insulin more than 3 months prior to screening is allowable, b) glucagon-like peptide 1 (GLP-1) analogs within 3 months prior to this screening, c) drugs to cause weight loss within 3 months prior to screening, d) thiazolidinediones (TZDs) within 3 months prior to screening, e) chronically treated (greater than or equal to 14 days) with an oral glucocorticoid or have received this type of therapy within 4 weeks prior to screening, or f) illegal drugs. * Have had 1 or more cases of uncontrolled diabetes that required hospitalization in the 6 months prior to screening. * Have stomach problems, have chronically taken medication to increase movement in the digestive tract or slow down the emptying of the digestive tract, or have had gastric bypass (bariatric) surgery. * Have had problems with the heart or brain in the past 2 months prior to screening, such as a heart attack, chest pain, heart failure, heart bypass operation, angioplasty or stent insertion, a heart rhythm problem, or a stroke. * Have a serum creatinine result which shows a greater than or equal to 1.5 milligrams per deciliter (mg/dL) for men or greater than or equal to 1.4 mg/dL for women. * Have a problem with the liver or pancreas. * Have a creatinine clearance result which shows less than 60 milliliters per minute (mL/min), evidence of a significant active, uncontrolled endocrine (hormone), or active autoimmune abnormality. * Have a serum calcitonin test which shows greater than or equal to 20 picograms per milliliter (pcg/mL) at the time of screening. * Have a family history of medullary C-cell hyperplasia or endocrine neoplasia type 2A or type 2B. * Have cancer (except for skin cancer) or have been in remission from cancer for less than 5 years. * Have had an organ transplant except for corneal transplant. * Have received treatment within the last 30 days with a drug which has not been regulatory approved. * Have participated in a medical, surgical, or pharmaceutical study where these types of procedures were performed within 30 days prior to screening. * Have any condition that is a contraindication to or would interfere with medications provided for this study to treat diabetes. * Have a blood disorder that would interfere with the drawing of blood glucose measurements or lab samples. * Have previously participated or signed an informed consent document for this same type of study and study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 26 weeks | Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication \[OAM\] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | 26 weeks and 52 weeks | The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, prior medication group, and treatment as factors included in the model. |
| Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose | Baseline, 26 weeks, and 52 weeks | Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect. |
| Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | Baseline, 26 weeks, and 52 weeks | The SMBG data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening; 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 analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline daily mean as a covariate. |
| Change From Baseline to 26 and 52 Weeks in Body Weight | Baseline, 26 weeks, and 52 weeks | Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline body weight as a covariate. |
| Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI) | Baseline, 26 weeks, and 52 weeks | Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline BMI as a covariate. |
| Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | Baseline, 26 weeks, and 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, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline HOMA2 as a covariate, and participant as a random effect. |
| Change From Baseline to 26 and 52 Weeks in Pulse Rate | Baseline, 26 weeks, and 52 weeks | Sitting pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. |
| Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score | Baseline, 26 weeks, and 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) adjusted by treatment, country, prior medication group, gender, and baseline score. |
| Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score | Baseline, 26 weeks, and 52 weeks | The Impact of Weight on Self-Perception (IW-SP) questionnaire contains 3 items that assess how often the participants' body weight affects how happy they are with their appearance and how often they feel self-conscious when out in public. Items are scored on a 5-point numeric rating scale where 5 = never and 1 = always. A single total score is calculated by summing the scores for all 3 items. Total score ranges between 3 and 15, where a higher score is indicative of better self-perception. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. |
| Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version | Baseline, 26 weeks, and 52 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). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. |
| Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version | 52 weeks | The Diabetes Treatment Satisfaction Questionnaire change (DTSQc) score is used to assess relative change in participant satisfaction from baseline. 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. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. |
| Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score | Baseline, 26 weeks, and 52 weeks | The Diabetes Symptoms Checklist-revised (DSC-r) was designed to assess the presence and perceived burden of diabetes-related symptoms. Respondents were to consider troublesomeness of 34 symptoms on a 5-point scale ranging from 5=extremely to 1=not at all. For symptoms/side-effects not experienced, the item was scored as 0. Symptoms were grouped into the following subscales: psychology-fatigue, psychology-cognitive, neurology-pain, neurology-sensory, cardiology, ophthalmology, hypoglycemia, and hyperglycemia. Subscale scores were calculated as the sum of the given subscale divided by the total number of items in the scale. Total score was computed from the sum of the 8 subscales and ranged from 0 to 40. Higher scores indicate greater symptom burden. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score. |
| Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks | 26 weeks and 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 26 and 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 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | Baseline, 26 weeks, and 52 weeks | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. |
| Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | Baseline, 52 weeks | Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication \[OAM\] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate. |
| Change From Baseline to 26 and 52 Weeks in Blood Pressure | Baseline, 26 weeks, and 52 weeks | Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect. |
| Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol | Baseline, 26 weeks, and 52 weeks | Percent changes in total cholesterol were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. |
| Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C) | Baseline, 26 weeks, and 52 weeks | Percentage changes in HDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. |
| Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C) | Baseline, 26 weeks, and 52 weeks | Percentage changes in LDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. |
| Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides | Baseline, 26 weeks, and 52 weeks | Percentage changes in triglycerides were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model. |
| Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Baseline, 26 weeks, and 52 weeks | Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured. |
| Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | Baseline, 26 weeks, and 52 weeks | — |
| Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies | Baseline through 52 weeks | A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The total number of treatment emergent ADA was not analyzed at 26 weeks. |
| Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Baseline through 26 weeks and 52 weeks | Hypoglycemic events 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 70 milligrams per deciliter \[mg/dL\]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). 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 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 70 milligrams per deciliter \[mg/dL\]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up | Baseline through 52 weeks plus 30-day follow up | The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Baseline through 52 weeks plus 30-day follow up | 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. 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 plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module. |
| Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC) | 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. |
| Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | Baseline, 26 weeks, and 52 weeks | Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects and baseline interval as a covariate. |
Countries
Argentina, Brazil, Canada, Croatia, Czechia, Finland, France, Germany, India, Mexico, Poland, Puerto Rico, Romania, Slovakia, South Africa, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.5 mg LY2189265 LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks | 269 |
| 0.75 mg LY2189265 LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneously (SC), once weekly for 52 weeks
Placebo: orally, twice daily for 52 weeks | 270 |
| Metformin Metformin: 2000 milligrams per day (mg/day) or at least 1500 mg/day, orally, for 52 weeks
Placebo: subcutaneously (SC), once weekly for 52 weeks | 268 |
| Total | 807 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 14 | 8 | 12 |
| Overall Study | Entry Criteria Not Met | 1 | 1 | 2 |
| Overall Study | Lack of Efficacy | 2 | 3 | 4 |
| Overall Study | Lost to Follow-up | 15 | 13 | 9 |
| Overall Study | Physician Decision | 1 | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 2 |
| Overall Study | Sponsor Decision | 5 | 4 | 7 |
| Overall Study | Treatment Non-compliance | 0 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 11 | 19 | 14 |
Baseline characteristics
| Characteristic | 0.75 mg LY2189265 | Total | 1.5 mg LY2189265 | Metformin |
|---|---|---|---|---|
| Age, Continuous | 55.90 years STANDARD_DEVIATION 10.68 | 55.56 years STANDARD_DEVIATION 10.38 | 55.51 years STANDARD_DEVIATION 10.38 | 55.26 years STANDARD_DEVIATION 10.1 |
| Body Mass Index (BMI) | 33.08 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.84 | 33.26 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.53 | 33.66 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.65 | 33.05 kilograms per square meter (kg/m^2) STANDARD_DEVIATION 5.06 |
| Body Weight | 91.79 kilograms (kg) STANDARD_DEVIATION 18.67 | 92.28 kilograms (kg) STANDARD_DEVIATION 18.87 | 92.67 kilograms (kg) STANDARD_DEVIATION 18.79 | 92.40 kilograms (kg) STANDARD_DEVIATION 19.23 |
| Duration of Diabetes | 2.60 years STANDARD_DEVIATION 2.17 | 2.63 years STANDARD_DEVIATION 1.83 | 2.65 years STANDARD_DEVIATION 1.5 | 2.63 years STANDARD_DEVIATION 1.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 87 Participants | 272 Participants | 90 Participants | 95 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 183 Participants | 535 Participants | 179 Participants | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Glycosylated Hemoglobin (HbA1c) | 7.58 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.87 | 7.60 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.87 | 7.63 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.92 | 7.60 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 28 Participants | 85 Participants | 29 Participants | 28 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 61 Participants | 21 Participants | 20 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 53 Participants | 17 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 7 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 198 Participants | 600 Participants | 201 Participants | 201 Participants |
| Region of Enrollment Argentina | 27 participants | 80 participants | 27 participants | 26 participants |
| Region of Enrollment Brazil | 2 participants | 7 participants | 2 participants | 3 participants |
| Region of Enrollment Canada | 9 participants | 30 participants | 10 participants | 11 participants |
| Region of Enrollment Croatia | 4 participants | 11 participants | 3 participants | 4 participants |
| Region of Enrollment Czech Republic | 9 participants | 27 participants | 10 participants | 8 participants |
| Region of Enrollment Finland | 5 participants | 12 participants | 3 participants | 4 participants |
| Region of Enrollment France | 12 participants | 37 participants | 12 participants | 13 participants |
| Region of Enrollment Germany | 21 participants | 64 participants | 22 participants | 21 participants |
| Region of Enrollment India | 11 participants | 29 participants | 9 participants | 9 participants |
| Region of Enrollment Korea, Republic of | 4 participants | 12 participants | 3 participants | 5 participants |
| Region of Enrollment Mexico | 25 participants | 72 participants | 24 participants | 23 participants |
| Region of Enrollment Poland | 6 participants | 18 participants | 7 participants | 5 participants |
| Region of Enrollment Puerto Rico | 10 participants | 39 participants | 14 participants | 15 participants |
| Region of Enrollment Romania | 13 participants | 40 participants | 14 participants | 13 participants |
| Region of Enrollment Slovakia | 9 participants | 26 participants | 8 participants | 9 participants |
| Region of Enrollment South Africa | 11 participants | 35 participants | 12 participants | 12 participants |
| Region of Enrollment Spain | 11 participants | 35 participants | 12 participants | 12 participants |
| Region of Enrollment United Kingdom | 1 participants | 2 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 80 participants | 231 participants | 77 participants | 74 participants |
| Sex: Female, Male Female | 152 Participants | 454 Participants | 155 Participants | 147 Participants |
| Sex: Female, Male Male | 118 Participants | 353 Participants | 114 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 177 / 269 | 178 / 270 | 170 / 268 |
| serious Total, serious adverse events | 15 / 269 | 20 / 270 | 16 / 268 |
Outcome results
Primary
Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication \[OAM\] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, 26 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.78 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| 0.75 mg LY2189265 | Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.71 percentage of glycosylated hemoglobin | Standard Error 0.06 |
| Metformin | Change From Baseline to 26-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.56 percentage of glycosylated hemoglobin | Standard Error 0.06 |
Comparison: The study was designed with 90% power to detect non-inferiority of 1.5 mg LY2189265 vs Metformin on HbA1c change from baseline at the 26-week primary endpoint with a margin of 0.4%, a standard deviation of 1.3%, and a 2-sided alpha of 0.05 assuming no true difference between treatments. This corresponds to 223 participants per arm, with an assumed drop-out rate of 11%.p-value: <0.00195% CI: [-0.36, -0.08]ANCOVA
p-value: <0.00195% CI: [-0.29, -0.01]ANCOVA
Comparison: Superiority analysis.p-value: 0.00295% CI: [-0.36, -0.08]ANCOVA
Comparison: Superiority analysis.p-value: 0.0295% CI: [-0.29, -0.01]ANCOVA
Secondary
Change From Baseline to 26 and 52 Weeks in Blood Pressure
Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable blood pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 26 weeks (n=244, 251, 239) | -1.89 milliliters of mercury (mmHg) | Standard Error 0.89 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 52 weeks (n=221, 219, 215) | -0.11 milliliters of mercury (mmHg) | Standard Error 0.88 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 26 weeks (n=244, 251, 239) | 0.05 milliliters of mercury (mmHg) | Standard Error 0.57 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 52 weeks (n=221, 219, 215) | 0.31 milliliters of mercury (mmHg) | Standard Error 0.6 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 52 weeks (n=221, 219, 215) | -1.37 milliliters of mercury (mmHg) | Standard Error 0.59 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 26 weeks (n=244, 251, 239) | -2.61 milliliters of mercury (mmHg) | Standard Error 0.88 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 26 weeks (n=244, 251, 239) | -1.02 milliliters of mercury (mmHg) | Standard Error 0.56 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 52 weeks (n=221, 219, 215) | -2.74 milliliters of mercury (mmHg) | Standard Error 0.88 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 26 weeks (n=244, 251, 239) | -0.64 milliliters of mercury (mmHg) | Standard Error 0.58 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 52 weeks (n=221, 219, 215) | -0.98 milliliters of mercury (mmHg) | Standard Error 0.88 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Blood Pressure | DBP, 52 weeks (n=221, 219, 215) | -0.38 milliliters of mercury (mmHg) | Standard Error 0.6 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Blood Pressure | SBP, 26 weeks (n=244, 251, 239) | -0.91 milliliters of mercury (mmHg) | Standard Error 0.89 |
Secondary
Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI)
Body mass index is an estimate of body fat based on body weight divided by height squared. Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline BMI as a covariate.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable BMI data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI) | 26 weeks | -0.86 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI) | 52 weeks | -0.73 kilograms per meter squared (kg/m^2) | Standard Error 0.11 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI) | 26 weeks | -0.51 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI) | 52 weeks | -0.42 kilograms per meter squared (kg/m^2) | Standard Error 0.1 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI) | 26 weeks | -0.82 kilograms per meter squared (kg/m^2) | Standard Error 0.09 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Body Mass Index (BMI) | 52 weeks | -0.83 kilograms per meter squared (kg/m^2) | Standard Error 0.11 |
p-value: 0.75ANCOVA
p-value: 0.003ANCOVA
p-value: 0.412ANCOVA
p-value: 0.001ANCOVA
Secondary
Change From Baseline to 26 and 52 Weeks in Body Weight
Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline body weight as a covariate.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable body weight data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 26 weeks (n=267, 269, 267) | -2.29 kilograms (kg) | Standard Error 0.24 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 52 weeks (n=267, 269, 267) | -1.93 kilograms (kg) | Standard Error 0.29 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 26 weeks (n=267, 269, 267) | -1.36 kilograms (kg) | Standard Error 0.24 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Body Weight | 52 weeks (n=267, 269, 267) | -1.09 kilograms (kg) | Standard Error 0.29 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Body Weight | 26 weeks (n=267, 269, 267) | -2.22 kilograms (kg) | Standard Error 0.24 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Body Weight | 52 weeks (n=267, 269, 267) | -2.20 kilograms (kg) | Standard Error 0.29 |
p-value: 0.811ANCOVA
p-value: 0.003ANCOVA
p-value: 0.44ANCOVA
p-value: 0.001ANCOVA
Secondary
Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles
The SMBG data were collected at the following 8 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening; 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 analysis of covariance (ANCOVA) with country, treatment, and prior medication group as fixed effects and baseline daily mean as a covariate.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable SMBG data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 26 weeks (n=195, 200, 211) | -1.98 millimoles per liter (mmol/L) | Standard Error 0.15 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 52 weeks (n=197, 200, 212) | -1.99 millimoles per liter (mmol/L) | Standard Error 0.16 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 26 weeks (n=195, 200, 211) | -1.75 millimoles per liter (mmol/L) | Standard Error 0.14 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 52 weeks (n=197, 200, 212) | -1.71 millimoles per liter (mmol/L) | Standard Error 0.16 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 26 weeks (n=195, 200, 211) | -1.68 millimoles per liter (mmol/L) | Standard Error 0.14 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles | 52 weeks (n=197, 200, 212) | -1.58 millimoles per liter (mmol/L) | Standard Error 0.15 |
p-value: 0.061ANCOVA
p-value: 0.647ANCOVA
p-value: 0.022ANCOVA
p-value: 0.469ANCOVA
Secondary
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTc = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin 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 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=230, 237, 221) | 2.60 milliseconds (msec) | Standard Error 1.17 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n=212, 212, 205) | 3.76 milliseconds (msec) | Standard Error 1.2 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=226, 235, 218) | -0.04 milliseconds (msec) | Standard Error 1.12 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=209, 210, 201) | 1.15 milliseconds (msec) | Standard Error 1.18 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=209, 210, 201) | 1.53 milliseconds (msec) | Standard Error 1.17 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=230, 237, 221) | 1.38 milliseconds (msec) | Standard Error 1.16 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=226, 235, 218) | -0.01 milliseconds (msec) | Standard Error 1.1 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n=212, 212, 205) | 0.73 milliseconds (msec) | Standard Error 1.19 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 52 weeks (n=209, 210, 201) | -2.88 milliseconds (msec) | Standard Error 1.19 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 52 weeks (n=212, 212, 205) | -0.53 milliseconds (msec) | Standard Error 1.21 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR interval, 26 weeks (n=226, 235, 218) | -2.04 milliseconds (msec) | Standard Error 1.13 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF interval, 26 weeks (n=230, 237, 221) | -0.91 milliseconds (msec) | Standard Error 1.18 |
Secondary
Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate
Electrocardiogram (ECG) heart rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects and baseline interval as a covariate.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable ECG heart rate data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 26 weeks (n=230, 237, 221) | 1.60 beats per minute (bpm) | Standard Error 0.6 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 52 weeks (n=212, 212, 205) | 2.02 beats per minute (bpm) | Standard Error 0.66 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 26 weeks (n=230, 237, 221) | 2.57 beats per minute (bpm) | Standard Error 0.59 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 52 weeks (n=212, 212, 205) | 2.36 beats per minute (bpm) | Standard Error 0.66 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 26 weeks (n=230, 237, 221) | 0.82 beats per minute (bpm) | Standard Error 0.61 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Electrocardiogram Parameters, Heart Rate | 52 weeks (n=212, 212, 205) | 1.27 beats per minute (bpm) | Standard Error 0.67 |
Secondary
Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose
Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable fasting blood glucose data. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose | 26 weeks (n=244, 247, 245) | -1.61 millimoles per liter (mmol/L) | Standard Error 0.13 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose | 52 weeks (n=207, 210, 194) | -1.56 millimoles per liter (mmol/L) | Standard Error 0.14 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose | 26 weeks (n=244, 247, 245) | -1.46 millimoles per liter (mmol/L) | Standard Error 0.13 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose | 52 weeks (n=207, 210, 194) | -1.00 millimoles per liter (mmol/L) | Standard Error 0.14 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose | 26 weeks (n=244, 247, 245) | -1.34 millimoles per liter (mmol/L) | Standard Error 0.13 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Fasting Blood Glucose | 52 weeks (n=207, 210, 194) | -1.15 millimoles per liter (mmol/L) | Standard Error 0.14 |
p-value: 0.451Mixed Models Analysis
p-value: 0.025Mixed Models Analysis
p-value: 0.402Mixed Models Analysis
p-value: 0.079Mixed Models Analysis
Secondary
Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function
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, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline HOMA2 as a covariate, and participant as a random effect.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin 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 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%B, 26 weeks (n=207, 207, 215) | 36.55 percentage of HOMA2 | Standard Error 3.42 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%B, 52 weeks (n=179, 185, 170) | 29.97 percentage of HOMA2 | Standard Error 3.46 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%S, 26 weeks (n=207, 207, 215) | 0.95 percentage of HOMA2 | Standard Error 2.29 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%S, 52 weeks (n=179, 185, 170) | 5.29 percentage of HOMA2 | Standard Error 2.43 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%S, 52 weeks (n=179, 185, 170) | 1.84 percentage of HOMA2 | Standard Error 2.43 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%B, 26 weeks (n=207, 207, 215) | 28.96 percentage of HOMA2 | Standard Error 3.44 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%S, 26 weeks (n=207, 207, 215) | 2.71 percentage of HOMA2 | Standard Error 2.29 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%B, 52 weeks (n=179, 185, 170) | 22.5 percentage of HOMA2 | Standard Error 3.46 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%S, 52 weeks (n=179, 185, 170) | 10.83 percentage of HOMA2 | Standard Error 2.48 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%B, 52 weeks (n=179, 185, 170) | 9.77 percentage of HOMA2 | Standard Error 3.51 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%S, 26 weeks (n=207, 207, 215) | 9.99 percentage of HOMA2 | Standard Error 2.25 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Homeostasis Model Assessment of Beta-cell Function | HOMA2-%B, 26 weeks (n=207, 207, 215) | 14.11 percentage of HOMA2 | Standard Error 3.37 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
p-value: 0.003Mixed Models Analysis
p-value: 0.001Mixed Models Analysis
p-value: 0.01Mixed Models Analysis
p-value: 0.077Mixed Models Analysis
p-value: 0.004Mixed Models Analysis
Secondary
Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes
Amylase (total and pancreas-derived \[PD\]) and lipase concentrations were measured.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable pancreatic enzyme data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 26 weeks | 7.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 52 weeks | 5.50 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 26 weeks | 5.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 52 weeks | 4.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 26 weeks | 7.00 units per liter (U/L) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 52 weeks | 5.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 52 weeks | 5.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 26 weeks | 6.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 52 weeks | 3.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 26 weeks | 5.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 52 weeks | 5.00 units per liter (U/L) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 26 weeks | 4.00 units per liter (U/L) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 52 weeks | 4.00 units per liter (U/L) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 26 weeks | 1.00 units per liter (U/L) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 52 weeks | 1.00 units per liter (U/L) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (PD), 52 weeks | 2.00 units per liter (U/L) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Amylase (total), 26 weeks | 4.00 units per liter (U/L) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pancreatic Enzymes | Lipase, 26 weeks | 1.00 units per liter (U/L) |
Secondary
Change From Baseline to 26 and 52 Weeks in Pulse Rate
Sitting pulse rate was measured. Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with treatment, country, prior medication group, visit, and treatment-by-visit interaction as fixed effects, baseline interval as a covariate, and participant as a random effect.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable pulse rate data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 26 weeks (n=244, 251, 239) | 2.39 beats per minute (bpm) | Standard Error 0.58 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 52 weeks (n=221, 219, 215) | 1.84 beats per minute (bpm) | Standard Error 0.57 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 26 weeks (n=244, 251, 239) | 2.14 beats per minute (bpm) | Standard Error 0.57 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 52 weeks (n=221, 219, 215) | 1.63 beats per minute (bpm) | Standard Error 0.57 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 26 weeks (n=244, 251, 239) | 1.59 beats per minute (bpm) | Standard Error 0.58 |
| Metformin | Change From Baseline to 26 and 52 Weeks in Pulse Rate | 52 weeks (n=221, 219, 215) | 1.12 beats per minute (bpm) | Standard Error 0.57 |
Secondary
Change From Baseline to 26 and 52 Weeks in Serum Calcitonin
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable serum calcitonin data. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 26 weeks | 0.00 picograms per milliliter (pcg/mL) |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 52 weeks | 0.00 picograms per milliliter (pcg/mL) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 26 weeks | 0.00 picograms per milliliter (pcg/mL) |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 52 weeks | 0.00 picograms per milliliter (pcg/mL) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 52 weeks | 0.00 picograms per milliliter (pcg/mL) |
| Metformin | Change From Baseline to 26 and 52 Weeks in Serum Calcitonin | 26 weeks | 0.00 picograms per milliliter (pcg/mL) |
Secondary
Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score
The Diabetes Symptoms Checklist-revised (DSC-r) was designed to assess the presence and perceived burden of diabetes-related symptoms. Respondents were to consider troublesomeness of 34 symptoms on a 5-point scale ranging from 5=extremely to 1=not at all. For symptoms/side-effects not experienced, the item was scored as 0. Symptoms were grouped into the following subscales: psychology-fatigue, psychology-cognitive, neurology-pain, neurology-sensory, cardiology, ophthalmology, hypoglycemia, and hyperglycemia. Subscale scores were calculated as the sum of the given subscale divided by the total number of items in the scale. Total score was computed from the sum of the 8 subscales and ranged from 0 to 40. Higher scores indicate greater symptom burden. Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable DSC-r data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score | 26 weeks (n=245, 253, 248) | 0.24 units on a scale | Standard Error 0.36 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score | 52 weeks (n=247, 255, 249) | 0.49 units on a scale | Standard Error 0.39 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score | 26 weeks (n=245, 253, 248) | -0.16 units on a scale | Standard Error 0.35 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score | 52 weeks (n=247, 255, 249) | 0.42 units on a scale | Standard Error 0.39 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score | 26 weeks (n=245, 253, 248) | 0.41 units on a scale | Standard Error 0.35 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Diabetes Symptoms Checklist Participant-reported Outcome (DSC-r) Score | 52 weeks (n=247, 255, 249) | 0.59 units on a scale | Standard Error 0.39 |
Secondary
Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status 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). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin 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 | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version | 26 weeks (n=244, 249, 241) | 1.93 units on a scale | Standard Error 0.39 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version | 52 weeks (n=245, 251, 244) | 1.82 units on a scale | Standard Error 0.44 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version | 26 weeks (n=244, 249, 241) | 1.81 units on a scale | Standard Error 0.38 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version | 52 weeks (n=245, 251, 244) | 1.29 units on a scale | Standard Error 0.43 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version | 26 weeks (n=244, 249, 241) | 2.04 units on a scale | Standard Error 0.39 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Status Version | 52 weeks (n=245, 251, 244) | 1.94 units on a scale | Standard Error 0.44 |
Secondary
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score
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) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable APPADL data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score | 26 weeks (n=247, 251, 247) | 0.09 units on a scale | Standard Error 0.33 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score | 52 weeks (n=247, 252, 248) | 0.39 units on a scale | Standard Error 0.33 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score | 26 weeks (n=247, 251, 247) | 0.19 units on a scale | Standard Error 0.32 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score | 52 weeks (n=247, 252, 248) | -0.05 units on a scale | Standard Error 0.33 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score | 26 weeks (n=247, 251, 247) | 0.02 units on a scale | Standard Error 0.32 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Activities of Daily Living (IW-ADL) Score | 52 weeks (n=247, 252, 248) | 0.28 units on a scale | Standard Error 0.33 |
Secondary
Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score
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) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable IW-SP data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score | 26 weeks (n=248, 254, 249) | 0.72 units on a scale | Standard Error 0.19 |
| 1.5 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score | 52 weeks (n=249, 255, 250) | 0.45 units on a scale | Standard Error 0.19 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score | 26 weeks (n=248, 254, 249) | 0.63 units on a scale | Standard Error 0.18 |
| 0.75 mg LY2189265 | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score | 52 weeks (n=249, 255, 250) | 0.61 units on a scale | Standard Error 0.19 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score | 26 weeks (n=248, 254, 249) | 0.79 units on a scale | Standard Error 0.18 |
| Metformin | Change From Baseline to 26 and 52 Weeks in the Impact of Weight on Self-Perception (IW-SP) Score | 52 weeks (n=249, 255, 250) | 0.75 units on a scale | Standard Error 0.19 |
Secondary
Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c)
Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country, treatment, and prior medication group (previous oral antihyperglycemic medication \[OAM\] versus no previous OAM) as fixed effects and baseline HbA1c as a covariate.
Time frame: Baseline, 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable HbA1c data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.70 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| 0.75 mg LY2189265 | Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.55 percentage of glycosylated hemoglobin | Standard Error 0.07 |
| Metformin | Change From Baseline to 52-week Endpoint in Glycosylated Hemoglobin (HbA1c) | -0.51 percentage of glycosylated hemoglobin | Standard Error 0.07 |
p-value: <0.00195% CI: [-0.35, -0.02]ANCOVA
p-value: <0.00195% CI: [-0.2, 0.12]ANCOVA
Comparison: Superiority analysis.p-value: 0.02495% CI: [-0.35, -0.02]ANCOVA
Comparison: Superiority analysis.p-value: 0.29995% CI: [-0.2, 0.12]ANCOVA
Secondary
Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version
The Diabetes Treatment Satisfaction Questionnaire change (DTSQc) score is used to assess relative change in participant satisfaction from baseline. 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. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 (much less satisfied) to +18 (much more satisfied). Least Squares (LS) means of change from baseline were calculated using analysis of covariance (ANCOVA) adjusted by treatment, country, prior medication group, gender, and baseline score.
Time frame: 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable DTSQc 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 | Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version | 12.92 units on a scale | Standard Error 0.52 |
| 0.75 mg LY2189265 | Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version | 12.73 units on a scale | Standard Error 0.5 |
| Metformin | Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score, Change Version | 12.58 units on a scale | Standard Error 0.51 |
Secondary
Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC)
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 received at least one dose of LY2189265 with evaluable LY2189265 concentration data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg LY2189265 | Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC) | 12036 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 5385 |
| 0.75 mg LY2189265 | Measurement of LY2189265 Drug Concentration for Pharmacokinetics: Area Under the Concentration Curve (AUC) | 5919 nanogram hours per milliliter (ng*hr/mL) | Standard Deviation 1548 |
Secondary
Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up
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. 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 plus 30-day follow up. 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 plus 30-day follow up
Population: Participants who received at least one dose of LY2189265 or Metformin.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any Fatal CV Event | 0 participants |
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any CV Event | 1 participants |
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any Nonfatal CV Event | 1 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any Fatal CV Event | 0 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any CV Event | 2 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any Nonfatal CV Event | 2 participants |
| Metformin | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any CV Event | 1 participants |
| Metformin | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any Nonfatal CV Event | 1 participants |
| Metformin | Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks Plus 30-day Follow up | Any Fatal CV Event | 0 participants |
Secondary
Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up
The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 52 weeks plus 30-day follow up. 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 plus 30-day follow up
Population: Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up | 0 participants |
| 0.75 mg LY2189265 | Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up | 0 participants |
| Metformin | Number of Participants With Adjudicated Pancreatitis at 52 Weeks Plus 30-day Follow up | 0 participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events at 26 and 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 26 and 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: 26 weeks and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks | 26 weeks | 163 participants |
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks | 52 weeks | 179 participants |
| 0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks | 26 weeks | 150 participants |
| 0.75 mg LY2189265 | Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks | 52 weeks | 177 participants |
| Metformin | Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks | 26 weeks | 151 participants |
| Metformin | Number of Participants With Treatment Emergent Adverse Events at 26 and 52 Weeks | 52 weeks | 170 participants |
Secondary
Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies
A participant was considered to have treatment emergent LY2189265 anti-drug antibodies (ADA) if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The total number of treatment emergent ADA was not analyzed at 26 weeks.
Time frame: Baseline through 52 weeks
Population: Participants who received at least one dose of LY2189265 with evaluable LY2189265 ADA data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg LY2189265 | Number of Participants With Treatment Emergent Anti-LY2189265 Antibodies | 10 participants |
Secondary
Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks
Hypoglycemic events 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 70 milligrams per deciliter \[mg/dL\]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 weeks and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin. Only pre-rescue measurements were used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Severe, 26 weeks (n=241, 248, 236) | 0 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Severe, 52 weeks (n=214, 217, 199) | 0 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Documented Symptomatic, 26 weeks (n=241, 248, 236) | 2 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Documented Symptomatic, 52 weeks (n=214, 217, 199) | 7 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Asymptomatic, 26 weeks (n=241, 248, 236) | 19 events |
| 1.5 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Asymptomatic, 52 weeks (n=214, 217, 199) | 5 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Documented Symptomatic, 52 weeks (n=214, 217, 199) | 8 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Severe, 26 weeks (n=241, 248, 236) | 0 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Documented Symptomatic, 26 weeks (n=241, 248, 236) | 6 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Asymptomatic, 52 weeks (n=214, 217, 199) | 9 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Severe, 52 weeks (n=214, 217, 199) | 0 events |
| 0.75 mg LY2189265 | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Asymptomatic, 26 weeks (n=241, 248, 236) | 9 events |
| Metformin | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Severe, 52 weeks (n=214, 217, 199) | 0 events |
| Metformin | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Documented Symptomatic, 26 weeks (n=241, 248, 236) | 2 events |
| Metformin | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Asymptomatic, 26 weeks (n=241, 248, 236) | 13 events |
| Metformin | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Asymptomatic, 52 weeks (n=214, 217, 199) | 9 events |
| Metformin | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Documented Symptomatic, 52 weeks (n=214, 217, 199) | 2 events |
| Metformin | Number of Self-reported Hypoglycemic Events at 26 and 52 Weeks | Severe, 26 weeks (n=241, 248, 236) | 0 events |
Secondary
Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C)
Percentage changes in HDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable HDL-C 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 | Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C) | 26 weeks (n=246, 244, 244) | 2.39 percentage change in HDL-C |
| 1.5 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C) | 52 weeks (n=248, 248, 246) | 4.95 percentage change in HDL-C |
| 0.75 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C) | 26 weeks (n=246, 244, 244) | 4.20 percentage change in HDL-C |
| 0.75 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C) | 52 weeks (n=248, 248, 246) | 2.31 percentage change in HDL-C |
| Metformin | Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C) | 26 weeks (n=246, 244, 244) | 5.78 percentage change in HDL-C |
| Metformin | Percentage Change From Baseline to 26 and 52 Weeks in High Density Lipoprotein Cholesterol (HDL-C) | 52 weeks (n=248, 248, 246) | 4.32 percentage change in HDL-C |
Secondary
Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C)
Percentage changes in LDL-C were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable LDL-C 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 | Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C) | 26 weeks (n=233, 231, 221) | -6.86 percentage change in LDL-C |
| 1.5 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C) | 52 weeks (n=236, 240, 231) | -2.06 percentage change in LDL-C |
| 0.75 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C) | 26 weeks (n=233, 231, 221) | -2.70 percentage change in LDL-C |
| 0.75 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C) | 52 weeks (n=236, 240, 231) | -2.34 percentage change in LDL-C |
| Metformin | Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C) | 26 weeks (n=233, 231, 221) | -8.97 percentage change in LDL-C |
| Metformin | Percentage Change From Baseline to 26 and 52 Weeks in Low Density Lipoprotein Cholesterol (LDL-C) | 52 weeks (n=236, 240, 231) | -7.23 percentage change in LDL-C |
Secondary
Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides
Percentage changes in triglycerides were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable triglyceride 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 | Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides | 26 weeks (n=252, 252, 253) | -2.35 percentage change in triglycerides |
| 1.5 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides | 52 weeks (n=255, 256, 254) | -4.27 percentage change in triglycerides |
| 0.75 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides | 26 weeks (n=252, 252, 253) | -1.96 percentage change in triglycerides |
| 0.75 mg LY2189265 | Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides | 52 weeks (n=255, 256, 254) | -0.86 percentage change in triglycerides |
| Metformin | Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides | 26 weeks (n=252, 252, 253) | 2.56 percentage change in triglycerides |
| Metformin | Percentage Change From Baseline to 26 and 52 Weeks in Triglycerides | 52 weeks (n=255, 256, 254) | 1.91 percentage change in triglycerides |
Secondary
Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks
The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% was analyzed with a logistic regression model with baseline, prior medication group, and treatment as factors included in the model.
Time frame: 26 weeks and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin 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 Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than 7%, 26 weeks | 61.5 percentage of participants |
| 1.5 mg LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than or equal to 6.5%, 26 weeks | 46.0 percentage of participants |
| 1.5 mg LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than 7%, 52 weeks | 60.0 percentage of participants |
| 1.5 mg LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than or equal to 6.5%, 52 weeks | 42.3 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than or equal to 6.5%, 52 weeks | 34.7 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than 7%, 26 weeks | 62.6 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than 7%, 52 weeks | 53.2 percentage of participants |
| 0.75 mg LY2189265 | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than or equal to 6.5%, 26 weeks | 40.0 percentage of participants |
| Metformin | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than or equal to 6.5%, 52 weeks | 28.3 percentage of participants |
| Metformin | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than or equal to 6.5%, 26 weeks | 29.8 percentage of participants |
| Metformin | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than 7%, 52 weeks | 48.3 percentage of participants |
| Metformin | Percentage of Participants Achieving a Glycosylated Hemoglobin (HbA1c) of Less Than 7% and Less Than or Equal to 6.5% at 26 and 52 Weeks | HbA1c less than 7%, 26 weeks | 53.6 percentage of participants |
p-value: 0.023Regression, Logistic
p-value: 0.021Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: 0.011Regression, Logistic
p-value: 0.001Regression, Logistic
p-value: 0.269Regression, Logistic
p-value: <0.001Regression, Logistic
p-value: 0.134Regression, Logistic
Secondary
Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol
Percent changes in total cholesterol were assessed using analysis of variance (ANOVA) on the rank-transformed data with only treatment included in the model.
Time frame: Baseline, 26 weeks, and 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin with evaluable cholesterol 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 | Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol | 26 weeks (n=244, 244, 243) | -3.86 percentage change in total cholesterol |
| 1.5 mg LY2189265 | Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol | 52 weeks (n=247, 248, 245) | -1.69 percentage change in total cholesterol |
| 0.75 mg LY2189265 | Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol | 26 weeks (n=244, 244, 243) | -1.77 percentage change in total cholesterol |
| 0.75 mg LY2189265 | Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol | 52 weeks (n=247, 248, 245) | -0.78 percentage change in total cholesterol |
| Metformin | Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol | 26 weeks (n=244, 244, 243) | -3.51 percentage change in total cholesterol |
| Metformin | Percent Change From Baseline to 26 and 52 Weeks in Total Cholesterol | 52 weeks (n=247, 248, 245) | -3.88 percentage change in total cholesterol |
Secondary
Rate of Self-reported Hypoglycemic Events at 52 Weeks
Hypoglycemic events 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 70 milligrams per deciliter \[mg/dL\]), or asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 70 mg/dL). The 1-year adjusted rate of hypoglycemic events is summarized cumulatively at 52 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 52 weeks
Population: Participants who received at least one dose of LY2189265 or Metformin. 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 | Documented Symptomatic | 0.62 events per participant per year | Standard Deviation 8.91 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Severe | 0.00 events per participant per year | Standard Deviation 0 |
| 1.5 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic | 0.24 events per participant per year | Standard Deviation 1.26 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Documented Symptomatic | 0.15 events per participant per year | Standard Deviation 0.72 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Severe | 0.00 events per participant per year | Standard Deviation 0 |
| 0.75 mg LY2189265 | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic | 0.30 events per participant per year | Standard Deviation 1.85 |
| Metformin | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Severe | 0.00 events per participant per year | Standard Deviation 0 |
| Metformin | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Asymptomatic | 0.18 events per participant per year | Standard Deviation 0.79 |
| Metformin | Rate of Self-reported Hypoglycemic Events at 52 Weeks | Documented Symptomatic | 0.09 events per participant per year | Standard Deviation 0.5 |