Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to examine if once-weekly dulaglutide is efficient and safe compared to glimepiride in participants with type 2 diabetes mellitus who have inadequate glycemic control with oral antihyperglycemic medication (OAM) or are OAM-naïve.
Interventions
DRUGDulaglutide
Administered SC
DRUGGlimepiride
Administered orally
DRUGPlacebo as Capsules
Placebo for glimepiride is administered orally as one to three capsules daily.
Placebo for dulaglutide is administered as one SC injection.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus * OAM-naïve or have been taking OAM monotherapy for at least 3 months * Glycosylated Hemoglobin (HbA1c) value of ≥7.0% to ≤10.5% for OAM-naïve participants or ≥6.5% to ≤10.0% for participants taking OAM monotherapy * Adult men or adult non-pregnant, non-breastfeeding women * Stable weight (±5%) ≥3 months prior to screening * Body mass index (BMI) of ≥19.0 to ≤35.0 kilograms per square meter (kg/m\^2)
Exclusion criteria
* Have type 1 diabetes mellitus * Have previously been treated with a glucagon-like peptide-1 (GLP-1) receptor agonist, GLP-1 analog, or any other incretin mimetic during the 3 months before screening * Are currently taking dipeptidylpeptidase-IV (DPP-IV) inhibitor and thiazolidinediones (TZD) during the 3 months before screening * Have gastric emptying abnormality * Have cardiac disorder defined as unstable angina, myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, heart failure, arrhythmia, transient ischemic attack, or stroke * Have poorly controlled hypertension (systolic blood pressure above 160 millimeters of mercury \[mmHg\] or diastolic blood pressure above 95 mmHg) * Have impaired liver function * Have impaired kidney function * Have history of chronic pancreatitis or acute pancreatitis * Have a serum calcitonin ≥20 picogram/milliliter (pg/mL) * Have a personal or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma or multiple endocrine neoplasia type 2 (MEN 2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at 26 Weeks | Baseline, 26 Weeks | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline HbA1c as covariate; and participant as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks | Baseline, 26 Weeks | FBG is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. FBG was measured by a central laboratory. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline FBG as covariate; and participant as a random effect. |
| Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Baseline, 26 Weeks | Change from baseline in mean daily blood glucose (BG) values were measured with a 7-point SMBG profile. Participants recorded their 7-point SMBG profiles on 2 separate, non-consecutive days during the 2-week period immediately before randomization, Week 8, Week 16, and Week 26 (or the Early Discontinuation Visit). The 7-point SMBG profile consisted of pre-prandial BG measures before the morning (fasting), midday, and evening meals; BG measures 2 hours after the start (post-prandial) of the morning, midday, and evening meals; and BG measures at bedtime. Mean at 26 weeks was assessed in all treatment groups. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect. |
| Rate of Hypoglycemic Episodes | Baseline through 26 Weeks | Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 milligrams per deciliter (mg/dL) (≤3.9 mmol/L). A severe hypoglycemic episode was defined as any hypoglycemic event for which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Log mean rates of total hypoglycemia (per 30 days per participant) are presented and were calculated from negative binomial regression model. The model included country/region, prior medication group, treatment, visit, and treatment-by-visit interaction. The logarithm of days between visits was adjusted as an offset to account for possible unequal duration between visits and between participants. |
| Number of Participants With Self-Reported Hypoglycemic Episodes | Baseline through 26 Weeks | The overall number of participants with self-reported hypoglycemic episodes is presented. |
| Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks | Baseline, up to 26 Weeks | Change from baseline in HOMA2-%B was assessed by using the homeostasis model assessment (HOMA) to quantify β-cell function. HOMA2-%B is a computer model that uses FBG, insulin, and C-peptide concentrations to estimate steady state β-cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means were calculated using an analysis of covariance (ANCOVA) model with country, baseline, pre-treatment, and treatment as fixed effects. |
| Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks | Baseline, up to 26 Weeks | Change from baseline in HOMA2-%S was assessed by using the HOMA to quantify insulin sensitivity. HOMA2-%S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means were calculated using an ANCOVA model with country, baseline, pre-treatment, and treatment as fixed effects. |
| Change From Baseline in Pancreatic Enzymes at 26 Weeks | Baseline, 26 Weeks | Amylase (total and pancreas-derived) and lipase concentrations were measured. |
| Change From Baseline in Serum Calcitonin at 26 Weeks | Baseline, 26 Weeks | — |
| Change From Baseline in Sitting Blood Pressure at 26 Weeks | Baseline, 26 Weeks | Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline blood pressure as covariate; and participant as a random effect. |
| Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks | 26 Weeks | Percentages of participants who achieved HbA1c levels of \<7% or ≤6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country. |
| Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks | Baseline, 26 Weeks | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and R-R wave (RR), which is the interval between two R waves. PR is the interval between the P wave and the ventricular depolarization wave (QRS) complex. |
| Change From Baseline in Heart Rate From ECG at 26 Weeks | Baseline, 26 Weeks | — |
| Change From Baseline in Body Weight at 26 Weeks | Baseline, 26 Weeks | LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect. |
| Change From Baseline in Body Mass Index (BMI) at 26 Weeks | Baseline, 26 Weeks | BMI is an estimate of body fat based on body weight divided by height squared. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect. |
| Percentage of Participants Developing Antibodies to Dulaglutide | Baseline through 26 Weeks | Dulaglutide anti-drug antibodies (ADA) were assessed at baseline and 26 weeks. A participant was considered to have treatment-emergent dulaglutide ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. |
| Number of Participants With Adjudicated Cardiovascular Events | Baseline through 26 Weeks | Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs that were adjudicated included myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention); and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious AEs regardless of causality, is located in the Reported Adverse Events module. |
| Number of Participants With Adjudicated Pancreatitis | Baseline through 26 Weeks | The number of adjudicated (by an independent committee of expert physicians) pancreatic events is summarized at 26 weeks. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
| European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Week 26 | The EQ-5D questionnaire is a widely used, generic questionnaire that assesses 5 dimensions associated with quality of life (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 possible levels of response: no problem, some problem, and extreme problem. Additional categories of response include ambiguous and missing. The number of participants per each of the 5 response categories is summarized for each of the 5 dimensions. |
| Visual Analog Scale (VAS) Score at 26 Weeks | Week 26 | The EQ-5D questionnaire is a widely used, generic questionnaire that assesses health-related quality of life and consists of a 100-milliliter (mm) visual analog scale (VAS) on which the participant rated their perceived health state on that day from 0-mm (worst imaginable health state) to 100-mm (best imaginable health state). |
| Change From Baseline in Sitting Pulse Rate at 26 Weeks | Baseline, 26 Weeks | LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline pulse rate as covariate; and participant as a random effect. |
Countries
China, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.5 mg Dulaglutide 1.5 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks. | 239 |
| 0.75 mg Dulaglutide 0.75 mg dulaglutide administered as one SC injection once-weekly plus one to three capsules of placebo each day for blinding purposes for up to 26 weeks. | 239 |
| Glimepiride 1 to 3 mg/day glimepiride administered orally as one to three capsules per day plus one SC injection of placebo once-weekly for blinding purposes for up to 26 weeks. | 242 |
| Total | 720 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 | 2 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 8 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 12 | 12 |
Baseline characteristics
| Characteristic | 1.5 mg Dulaglutide | 0.75 mg Dulaglutide | Glimepiride | Total |
|---|---|---|---|---|
| Age, Continuous | 52.69 years STANDARD_DEVIATION 10.754 | 53.79 years STANDARD_DEVIATION 10.093 | 51.97 years STANDARD_DEVIATION 10.052 | 52.81 years STANDARD_DEVIATION 10.317 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 239 Participants | 239 Participants | 242 Participants | 720 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 184 Participants | 186 Participants | 186 Participants | 556 Participants |
| Region of Enrollment South Korea | 26 Participants | 25 Participants | 27 Participants | 78 Participants |
| Region of Enrollment Taiwan | 29 Participants | 28 Participants | 29 Participants | 86 Participants |
| Sex: Female, Male Female | 105 Participants | 112 Participants | 112 Participants | 329 Participants |
| Sex: Female, Male Male | 134 Participants | 127 Participants | 130 Participants | 391 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 | 165 / 244 | 141 / 248 | 137 / 243 |
| serious Total, serious adverse events | 6 / 244 | 4 / 248 | 3 / 243 |
Outcome results
Primary
Change From Baseline in HbA1c at 26 Weeks
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline HbA1c as covariate; and participant as a random effect.
Time frame: Baseline, 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in HbA1c at 26 Weeks | -1.48 percentage of HbA1c | Standard Error 0.069 |
| 0.75 mg Dulaglutide | Change From Baseline in HbA1c at 26 Weeks | -1.22 percentage of HbA1c | Standard Error 0.069 |
| Glimepiride | Change From Baseline in HbA1c at 26 Weeks | -0.92 percentage of HbA1c | Standard Error 0.069 |
p-value: <0.00195% CI: [-0.76, -0.39]Mixed Models Analysis
p-value: <0.00195% CI: [-0.5, -0.13]Mixed Models Analysis
Secondary
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks
Change from baseline in mean daily blood glucose (BG) values were measured with a 7-point SMBG profile. Participants recorded their 7-point SMBG profiles on 2 separate, non-consecutive days during the 2-week period immediately before randomization, Week 8, Week 16, and Week 26 (or the Early Discontinuation Visit). The 7-point SMBG profile consisted of pre-prandial BG measures before the morning (fasting), midday, and evening meals; BG measures 2 hours after the start (post-prandial) of the morning, midday, and evening meals; and BG measures at bedtime. Mean at 26 weeks was assessed in all treatment groups. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect.
Time frame: Baseline, 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Morning (2 hours post-prandial) meal | -4.56 mmol/L | Standard Error 0.18 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Evening (pre-prandial) meal | -2.36 mmol/L | Standard Error 0.135 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Midday (2 hours post-prandial) meal | -4.15 mmol/L | Standard Error 0.174 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Morning (fasting) | -2.47 mmol/L | Standard Error 0.092 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Bedtime | -3.22 mmol/L | Standard Error 0.152 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Evening (2 hours post-prandial) meal | -3.63 mmol/L | Standard Error 0.164 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Midday (pre-prandial) meal | -3.09 mmol/L | Standard Error 0.151 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Midday (2 hours post-prandial) meal | -3.40 mmol/L | Standard Error 0.174 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Morning (fasting) | -1.91 mmol/L | Standard Error 0.092 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Morning (2 hours post-prandial) meal | -3.75 mmol/L | Standard Error 0.181 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Midday (pre-prandial) meal | -2.43 mmol/L | Standard Error 0.151 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Evening (pre-prandial) meal | -1.77 mmol/L | Standard Error 0.136 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Evening (2 hours post-prandial) meal | -2.80 mmol/L | Standard Error 0.165 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Bedtime | -2.69 mmol/L | Standard Error 0.152 |
| Glimepiride | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Evening (pre-prandial) meal | -1.69 mmol/L | Standard Error 0.134 |
| Glimepiride | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Morning (2 hours post-prandial) meal | -3.20 mmol/L | Standard Error 0.179 |
| Glimepiride | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Bedtime | -2.03 mmol/L | Standard Error 0.15 |
| Glimepiride | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Evening (2 hours post-prandial) meal | -2.35 mmol/L | Standard Error 0.164 |
| Glimepiride | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Midday (2 hours post-prandial) meal | -2.58 mmol/L | Standard Error 0.173 |
| Glimepiride | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Midday (pre-prandial) meal | -2.37 mmol/L | Standard Error 0.15 |
| Glimepiride | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks | Morning (fasting) | -1.80 mmol/L | Standard Error 0.091 |
p-value: <0.00195% CI: [-0.89, -0.45]Mixed Models Analysis
p-value: 0.30495% CI: [-0.34, 0.11]Mixed Models Analysis
p-value: <0.00195% CI: [-1.8, -0.92]Mixed Models Analysis
p-value: 0.01595% CI: [-0.99, -0.11]Mixed Models Analysis
p-value: <0.00195% CI: [-1.1, -0.36]Mixed Models Analysis
p-value: 0.7495% CI: [-0.43, 0.31]Mixed Models Analysis
p-value: <0.00195% CI: [-1.99, -1.13]Mixed Models Analysis
p-value: <0.00195% CI: [-1.24, -0.39]Mixed Models Analysis
p-value: <0.00195% CI: [-1, -0.34]Mixed Models Analysis
p-value: 0.63895% CI: [-0.41, 0.25]Mixed Models Analysis
p-value: <0.00195% CI: [-1.68, -0.87]Mixed Models Analysis
p-value: 0.0395% CI: [-0.85, -0.04]Mixed Models Analysis
p-value: <0.00195% CI: [-1.56, -0.82]Mixed Models Analysis
p-value: <0.00195% CI: [-1.03, -0.29]Mixed Models Analysis
Secondary
Change From Baseline in Body Mass Index (BMI) at 26 Weeks
BMI is an estimate of body fat based on body weight divided by height squared. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect.
Time frame: Baseline, 26 Weeks
Population: All participants who were randomized, received at least one dose of study drug, and had evaluable BMI data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Body Mass Index (BMI) at 26 Weeks | -0.55 kilograms per meter squared (kg/m^2) | Standard Error 0.07 |
| 0.75 mg Dulaglutide | Change From Baseline in Body Mass Index (BMI) at 26 Weeks | -0.29 kilograms per meter squared (kg/m^2) | Standard Error 0.07 |
| Glimepiride | Change From Baseline in Body Mass Index (BMI) at 26 Weeks | 0.32 kilograms per meter squared (kg/m^2) | Standard Error 0.069 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Body Weight at 26 Weeks
LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline body weight as covariate; and participant as a random effect.
Time frame: Baseline, 26 Weeks
Population: All participants who were randomized, received at least one dose of study drug, and had evaluable body weight data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Body Weight at 26 Weeks | -1.46 kilogram (kg) | Standard Error 0.192 |
| 0.75 mg Dulaglutide | Change From Baseline in Body Weight at 26 Weeks | -0.77 kilogram (kg) | Standard Error 0.192 |
| Glimepiride | Change From Baseline in Body Weight at 26 Weeks | 0.89 kilogram (kg) | Standard Error 0.19 |
p-value: <0.001Mixed Models Analysis
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR\^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and R-R wave (RR), which is the interval between two R waves. PR is the interval between the P wave and the ventricular depolarization wave (QRS) complex.
Time frame: Baseline, 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement, and had evaluable ECG data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks | QT interval | -6.18 milliseconds (msec) | Standard Deviation 21.469 |
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks | PR interval | 3.73 milliseconds (msec) | Standard Deviation 13.411 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks | QT interval | -2.06 milliseconds (msec) | Standard Deviation 19.549 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks | PR interval | 3.29 milliseconds (msec) | Standard Deviation 11.236 |
| Glimepiride | Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks | QT interval | 1.21 milliseconds (msec) | Standard Deviation 23.021 |
| Glimepiride | Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia Corrected QT (QTcF) Interval and P-R Wave (PR) Interval at 26 Weeks | PR interval | -0.23 milliseconds (msec) | Standard Deviation 10.184 |
Secondary
Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks
FBG is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. FBG was measured by a central laboratory. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline FBG as covariate; and participant as a random effect.
Time frame: Baseline, 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks | -2.71 millimoles per liter (mmol/L) | Standard Error 0.135 |
| 0.75 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks | -2.26 millimoles per liter (mmol/L) | Standard Error 0.137 |
| Glimepiride | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks | -1.89 millimoles per liter (mmol/L) | Standard Error 0.136 |
p-value: <0.00195% CI: [-1.15, -0.51]Mixed Models Analysis
p-value: 0.02295% CI: [-0.7, -0.05]Mixed Models Analysis
Secondary
Change From Baseline in Heart Rate From ECG at 26 Weeks
Time frame: Baseline, 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement, and had evaluable ECG data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Heart Rate From ECG at 26 Weeks | 3.99 bpm | Standard Deviation 8.459 |
| 0.75 mg Dulaglutide | Change From Baseline in Heart Rate From ECG at 26 Weeks | 1.90 bpm | Standard Deviation 8.046 |
| Glimepiride | Change From Baseline in Heart Rate From ECG at 26 Weeks | 0.44 bpm | Standard Deviation 9.275 |
Secondary
Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks
Change from baseline in HOMA2-%S was assessed by using the HOMA to quantify insulin sensitivity. HOMA2-%S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means were calculated using an ANCOVA model with country, baseline, pre-treatment, and treatment as fixed effects.
Time frame: Baseline, up to 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement. LOCF methodology was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks | Insulin-Based HOMA2-%S | -6.85 percentage of HOMA2-%S | Standard Error 2.636 |
| 1.5 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks | C-Peptide-Based HOMA2-%S | -6.44 percentage of HOMA2-%S | Standard Error 2.056 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks | Insulin-Based HOMA2-%S | -10.33 percentage of HOMA2-%S | Standard Error 2.662 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks | C-Peptide-Based HOMA2-%S | -11.84 percentage of HOMA2-%S | Standard Error 2.082 |
| Glimepiride | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks | Insulin-Based HOMA2-%S | -7.19 percentage of HOMA2-%S | Standard Error 2.602 |
| Glimepiride | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks | C-Peptide-Based HOMA2-%S | -5.05 percentage of HOMA2-%S | Standard Error 2.074 |
Comparison: Insulin-Based HOMA2%Sp-value: 0.91395% CI: [-5.83, 6.51]ANCOVA
Comparison: Insulin-Based HOMA2%Sp-value: 0.31895% CI: [-9.3, 3.03]ANCOVA
Comparison: C-Peptide-Based HOMA2-%Sp-value: 0.57695% CI: [-6.27, 3.49]ANCOVA
Comparison: C-Peptide-Based HOMA2-%Sp-value: 0.00795% CI: [-11.68, -1.89]ANCOVA
Secondary
Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks
Change from baseline in HOMA2-%B was assessed by using the homeostasis model assessment (HOMA) to quantify β-cell function. HOMA2-%B is a computer model that uses FBG, insulin, and C-peptide concentrations to estimate steady state β-cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means were calculated using an analysis of covariance (ANCOVA) model with country, baseline, pre-treatment, and treatment as fixed effects.
Time frame: Baseline, up to 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement. LOCF methodology was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks | Insulin-based HOMA-2%B | 47.40 percentage of HOMA2-%B | Standard Error 2.624 |
| 1.5 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks | C-peptide HOMA-2%B | 41.02 percentage of HOMA2-%B | Standard Error 1.945 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks | Insulin-based HOMA-2%B | 37.92 percentage of HOMA2-%B | Standard Error 2.664 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks | C-peptide HOMA-2%B | 34.57 percentage of HOMA2-%B | Standard Error 1.974 |
| Glimepiride | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks | Insulin-based HOMA-2%B | 30.00 percentage of HOMA2-%B | Standard Error 2.591 |
| Glimepiride | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β) - Cell Function (HOMA2-%B) at 26 Weeks | C-peptide HOMA-2%B | 24.58 percentage of HOMA2-%B | Standard Error 1.964 |
Comparison: Insulin HOMA2-%Bp-value: <0.00195% CI: [11.27, 23.55]ANCOVA
Comparison: Insulin HOMA2%Bp-value: 0.01295% CI: [1.78, 14.06]ANCOVA
Comparison: C-Peptide-Based HOMA2-%Bp-value: <0.00195% CI: [11.81, 21.06]ANCOVA
Comparison: C-Peptide-Based HOMA2-%Bp-value: <0.00195% CI: [5.36, 14.62]ANCOVA
Secondary
Change From Baseline in Pancreatic Enzymes at 26 Weeks
Amylase (total and pancreas-derived) and lipase concentrations were measured.
Time frame: Baseline, 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement and had evaluable pancreatic enzyme data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Pancreas-derived amylase | 6.19 units per liter (u/L) | Standard Deviation 12.824 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Total amylase | 9.29 units per liter (u/L) | Standard Deviation 16.237 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Lipase | 10.62 units per liter (u/L) | Standard Deviation 30.086 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Pancreas-derived amylase | 4.92 units per liter (u/L) | Standard Deviation 8.123 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Total amylase | 7.04 units per liter (u/L) | Standard Deviation 13.128 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Lipase | 9.28 units per liter (u/L) | Standard Deviation 22.651 |
| Glimepiride | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Total amylase | 3.79 units per liter (u/L) | Standard Deviation 12.538 |
| Glimepiride | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Lipase | 2.38 units per liter (u/L) | Standard Deviation 22.717 |
| Glimepiride | Change From Baseline in Pancreatic Enzymes at 26 Weeks | Pancreas-derived amylase | 2.64 units per liter (u/L) | Standard Deviation 8.218 |
Secondary
Change From Baseline in Serum Calcitonin at 26 Weeks
Time frame: Baseline, 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement, and had evaluable serum calcitonin data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Serum Calcitonin at 26 Weeks | -0.01 picomoles per liter (pmol/L) | Standard Deviation 0.318 |
| 0.75 mg Dulaglutide | Change From Baseline in Serum Calcitonin at 26 Weeks | -0.02 picomoles per liter (pmol/L) | Standard Deviation 0.298 |
| Glimepiride | Change From Baseline in Serum Calcitonin at 26 Weeks | 0.02 picomoles per liter (pmol/L) | Standard Deviation 1.193 |
Secondary
Change From Baseline in Sitting Blood Pressure at 26 Weeks
Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline blood pressure as covariate; and participant as a random effect.
Time frame: Baseline, 26 Weeks
Population: All participants who were randomized, received at least one dose of study drug, and had evaluable blood pressure data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Sitting Blood Pressure at 26 Weeks | SBP | -2.07 millimeters of mercury (mmHg) | Standard Error 0.815 |
| 1.5 mg Dulaglutide | Change From Baseline in Sitting Blood Pressure at 26 Weeks | DBP | -0.10 millimeters of mercury (mmHg) | Standard Error 0.535 |
| 0.75 mg Dulaglutide | Change From Baseline in Sitting Blood Pressure at 26 Weeks | SBP | -1.88 millimeters of mercury (mmHg) | Standard Error 0.813 |
| 0.75 mg Dulaglutide | Change From Baseline in Sitting Blood Pressure at 26 Weeks | DBP | -0.11 millimeters of mercury (mmHg) | Standard Error 0.534 |
| Glimepiride | Change From Baseline in Sitting Blood Pressure at 26 Weeks | SBP | -0.66 millimeters of mercury (mmHg) | Standard Error 0.804 |
| Glimepiride | Change From Baseline in Sitting Blood Pressure at 26 Weeks | DBP | 0.15 millimeters of mercury (mmHg) | Standard Error 0.526 |
p-value: 0.18Mixed Models Analysis
p-value: 0.245Mixed Models Analysis
p-value: 0.717Mixed Models Analysis
p-value: 0.619Mixed Models Analysis
Secondary
Change From Baseline in Sitting Pulse Rate at 26 Weeks
LS means were calculated using MMRM analysis adjusting for treatment, country, pre-study therapy stratum, visit, and treatment-by-visit as fixed effects; baseline pulse rate as covariate; and participant as a random effect.
Time frame: Baseline, 26 Weeks
Population: All participants who were randomized, received at least one dose of study drug, and had evaluable pulse rate data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Sitting Pulse Rate at 26 Weeks | 3.07 beats per minute (bpm) | Standard Error 0.581 |
| 0.75 mg Dulaglutide | Change From Baseline in Sitting Pulse Rate at 26 Weeks | 1.24 beats per minute (bpm) | Standard Error 0.581 |
| Glimepiride | Change From Baseline in Sitting Pulse Rate at 26 Weeks | -0.34 beats per minute (bpm) | Standard Error 0.572 |
p-value: <0.001Mixed Models Analysis
p-value: 0.035Mixed Models Analysis
Secondary
European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks
The EQ-5D questionnaire is a widely used, generic questionnaire that assesses 5 dimensions associated with quality of life (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 possible levels of response: no problem, some problem, and extreme problem. Additional categories of response include ambiguous and missing. The number of participants per each of the 5 response categories is summarized for each of the 5 dimensions.
Time frame: Week 26
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement, and had evaluable EQ-5D data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - some problems | 23 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - ambiguous | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - some problem | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - missing | 1 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - no problems | 208 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - extreme problem | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - some problems | 13 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - extreme problem | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - extreme problems | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - ambiguous | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - missing | 1 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - extreme problems | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - ambiguous | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - no problem | 217 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - missing | 1 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - ambiguous | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - no problems | 221 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - some problems | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - some problem | 4 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - extreme problems | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - missing | 1 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - ambiguous | 0 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - missing | 1 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - no problems | 198 participants |
| 1.5 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - no problem | 221 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - missing | 3 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - no problem | 220 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - extreme problems | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - no problem | 218 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - ambiguous | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - ambiguous | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - extreme problems | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - some problem | 3 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - missing | 3 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - some problem | 1 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - missing | 3 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - no problems | 214 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - some problems | 28 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - ambiguous | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - some problems | 7 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - no problems | 219 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - ambiguous | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - extreme problems | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - extreme problem | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - missing | 3 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - ambiguous | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - extreme problem | 0 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - some problems | 2 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - missing | 3 participants |
| 0.75 mg Dulaglutide | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - no problems | 192 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - missing | 1 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - no problem | 224 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - some problem | 6 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - extreme problem | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - ambiguous | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Mobility - missing | 1 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - no problem | 228 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - some problem | 2 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - extreme problem | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - ambiguous | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Self-care - missing | 1 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - no problems | 228 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - some problems | 2 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - extreme problems | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - ambiguous | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Usual activities - missing | 1 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - no problems | 200 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - some problems | 29 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - extreme problems | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - ambiguous | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Pain/Discomfort - missing | 1 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - no problems | 213 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - some problems | 17 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - extreme problems | 0 participants |
| Glimepiride | European Quality of Life Questionnaire-5 Dimensions (EQ-5D) Health State Score Responses at 26 Weeks | Anxiety/Depression - ambiguous | 0 participants |
Secondary
Number of Participants With Adjudicated Cardiovascular Events
Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular AEs that were adjudicated included myocardial infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention); and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious AEs regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline through 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg Dulaglutide | Number of Participants With Adjudicated Cardiovascular Events | 0 number of participants |
| 0.75 mg Dulaglutide | Number of Participants With Adjudicated Cardiovascular Events | 1 number of participants |
| Glimepiride | Number of Participants With Adjudicated Cardiovascular Events | 0 number of participants |
Secondary
Number of Participants With Adjudicated Pancreatitis
The number of adjudicated (by an independent committee of expert physicians) pancreatic events is summarized at 26 weeks. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg Dulaglutide | Number of Participants With Adjudicated Pancreatitis | 7 participants |
| 0.75 mg Dulaglutide | Number of Participants With Adjudicated Pancreatitis | 5 participants |
| Glimepiride | Number of Participants With Adjudicated Pancreatitis | 1 participants |
Secondary
Number of Participants With Self-Reported Hypoglycemic Episodes
The overall number of participants with self-reported hypoglycemic episodes is presented.
Time frame: Baseline through 26 Weeks
Population: All participants who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg Dulaglutide | Number of Participants With Self-Reported Hypoglycemic Episodes | 14 participants |
| 0.75 mg Dulaglutide | Number of Participants With Self-Reported Hypoglycemic Episodes | 9 participants |
| Glimepiride | Number of Participants With Self-Reported Hypoglycemic Episodes | 38 participants |
p-value: <0.001Fisher Exact
p-value: <0.001Fisher Exact
Secondary
Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks
Percentages of participants who achieved HbA1c levels of \<7% or ≤6.5% were analyzed using a logistic regression model, controlling for treatment, pre-treatment, baseline HbA1c and country.
Time frame: 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, and had at least one post-baseline HbA1c measurement. Last observation carried forward (LOCF) methodology was used to impute missing post-baseline values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks | HbA1c ≤6.5% | 59.4 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks | HbA1c <7.0% | 74.1 percentage of participants |
| 0.75 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks | HbA1c ≤6.5% | 47.7 percentage of participants |
| 0.75 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks | HbA1c <7.0% | 63.6 percentage of participants |
| Glimepiride | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks | HbA1c ≤6.5% | 41.3 percentage of participants |
| Glimepiride | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks | HbA1c <7.0% | 57.4 percentage of participants |
p-value: <0.0015% CI: [1.8, 4.1]Fisher Exact
p-value: <0.00195% CI: [1, 2.3]Fisher Exact
p-value: <0.00195% CI: [1.8, 4.5]Fisher Exact
p-value: 0.19295% CI: [1.1, 2.5]Fisher Exact
Secondary
Percentage of Participants Developing Antibodies to Dulaglutide
Dulaglutide anti-drug antibodies (ADA) were assessed at baseline and 26 weeks. A participant was considered to have treatment-emergent dulaglutide ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.
Time frame: Baseline through 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement, and had evaluable ADA data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg Dulaglutide | Percentage of Participants Developing Antibodies to Dulaglutide | 17 percentage of participants |
| 0.75 mg Dulaglutide | Percentage of Participants Developing Antibodies to Dulaglutide | 8 percentage of participants |
| Glimepiride | Percentage of Participants Developing Antibodies to Dulaglutide | 4 percentage of participants |
Secondary
Rate of Hypoglycemic Episodes
Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 milligrams per deciliter (mg/dL) (≤3.9 mmol/L). A severe hypoglycemic episode was defined as any hypoglycemic event for which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Log mean rates of total hypoglycemia (per 30 days per participant) are presented and were calculated from negative binomial regression model. The model included country/region, prior medication group, treatment, visit, and treatment-by-visit interaction. The logarithm of days between visits was adjusted as an offset to account for possible unequal duration between visits and between participants.
Time frame: Baseline through 26 Weeks
Population: Participants who had been randomized, received at least one dose of study drug, and had evaluable hypoglycemic data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Episodes | Severe Hypoglycemic Episodes | NA episodes/participant/30 days | — |
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Episodes | All Hypoglycemic Episodes | 0.01 episodes/participant/30 days | Standard Deviation 0.053 |
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Episodes | Nocturnal Hypoglycemic Episodes | 0.00 episodes/participant/30 days | Standard Deviation 0.011 |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Episodes | Severe Hypoglycemic Episodes | NA episodes/participant/30 days | — |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Episodes | All Hypoglycemic Episodes | 0.01 episodes/participant/30 days | Standard Deviation 0.041 |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Episodes | Nocturnal Hypoglycemic Episodes | 0.00 episodes/participant/30 days | Standard Deviation 0.01 |
| Glimepiride | Rate of Hypoglycemic Episodes | All Hypoglycemic Episodes | 0.09 episodes/participant/30 days | Standard Deviation 0.581 |
| Glimepiride | Rate of Hypoglycemic Episodes | Nocturnal Hypoglycemic Episodes | 0.01 episodes/participant/30 days | Standard Deviation 0.057 |
| Glimepiride | Rate of Hypoglycemic Episodes | Severe Hypoglycemic Episodes | NA episodes/participant/30 days | — |
p-value: <0.001Negative binomial regression model
p-value: <0.001Negative binomial regression model
p-value: 0.008Negative binomial regression model
p-value: 0.006Negative binomial regression model
Secondary
Visual Analog Scale (VAS) Score at 26 Weeks
The EQ-5D questionnaire is a widely used, generic questionnaire that assesses health-related quality of life and consists of a 100-milliliter (mm) visual analog scale (VAS) on which the participant rated their perceived health state on that day from 0-mm (worst imaginable health state) to 100-mm (best imaginable health state).
Time frame: Week 26
Population: Participants who had been randomized, received at least one dose of study drug, had a baseline HbA1c measurement, had at least one post-baseline HbA1c measurement, and had evaluable VAS data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Visual Analog Scale (VAS) Score at 26 Weeks | 85.72 units on a scale | Standard Deviation 9.723 |
| 0.75 mg Dulaglutide | Visual Analog Scale (VAS) Score at 26 Weeks | 86.17 units on a scale | Standard Deviation 10.744 |
| Glimepiride | Visual Analog Scale (VAS) Score at 26 Weeks | 85.96 units on a scale | Standard Deviation 10.938 |