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 once-daily insulin glargine in participants with type 2 diabetes mellitus who have inadequate glycemic control with 1 or 2 oral antihyperglycemic medications (OAM) (metformin and/or a sulfonylurea), in addition to any healthy lifestyle changes recommended by their healthcare providers.
Interventions
DRUGDulaglutide
Administered SC
DRUGInsulin glargine
Administered SC per dosing titration schedule
DRUGMetformin
Administered orally at pre-study prescribed dose, and is not being provided as part of the trial.
DRUGSulfonylureas
Administered orally at pre-study prescribed dose, and is not being provided as part of the trial.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes mellitus for at least 6 months * Have been taking metformin and/or a sulfonylurea for at least 3 months before screening and have been on a stable therapeutic dose for at least 8 weeks * Glycosylated hemoglobin (HbA1c) value of ≥7.0% to ≤11.0% * Adult men or adult non-pregnant, non-breastfeeding women * Body Mass Index (BMI) of ≥19.0 to ≤35.0 kilograms/square meter (kg/m\^2) * Stable weight (±5%) ≥3 months prior to screening
Exclusion criteria
* Have type 1 diabetes mellitus * Have previous treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist, GLP-1 analog, or any other incretin mimetic * Have treatment with dipeptidyl peptidase-IV (DPP-IV) inhibitor, an alpha-glucosidase inhibitor (AGI), thiazolidinedione (TZD), or glinide * 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 millimeter 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 picograms per 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 Glycosylated Hemoglobin (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 square (LS) means of change from baseline in HbA1c were calculated using a mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, baseline HbA1c, country, oral antihyperglycemic medication (OAM) , visit, and treatment-by-visit interaction as fixed effects, and participant was the random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | Up to 26 and 52 weeks | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. |
| Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks | Baseline, 26 Weeks, 52 Weeks | LS means of change from baseline were calculated using MMRM with the change in FBG as the dependent variable and treatment, baseline value, country, OAM, visit, and treatment-by-visit interaction as fixed effects, and participant was the random effect. |
| Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Baseline, 26 Weeks, 52 Weeks | Participants were required to perform 7-point SMBG profiles on 2 separate, nonconsecutive days during the 2 weeks before randomization and Weeks 8, 14, 20, 26, 39, and 52 (or the Early Discontinuation Visit). SMBG measurements were taken using a plasma-equivalent blood glucose (BG) meter at 7 time points: morning pre-meal, morning 2 hours post-meal, mid-day pre-meal, mid-day 2 hours post-meal, evening pre-meal, evening 2 hours post-meal, and at bedtime. Mean and Week 26 and Week 52 was assessed in all treatment groups. LS means of change from baseline were calculated using MMRM with the change in 7-point SMBG as the dependent variable and treatment, baseline value, country, OAM, visit, and treatment-by-visit interaction as fixed effects, and participant was the random effect. |
| Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weeks | Baseline, 26 weeks, 52 weeks | The updated Homeostasis Model Assessment (HOMA2) was used to quantify steady state beta-cell function (%B). HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate %B as a percentage of a normal reference population. LS means were calculated using a homeostasis model assessment with change from baseline in HOMA-%B as a covariate and country, baseline measurement, OAM, and treatment as fixed effects. |
| Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks and 52 Weeks | Baseline, 26 Weeks, 52 Weeks | The HOMA2 was used to estimate the steady-state insulin sensitivity (%S). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as a percentage of the normal reference population. LS means were calculated using an homeostasis model assessment with change from baseline in HOMA-%S as a covariate and country, baseline measurement, OAM, and treatment as fixed effects. |
| Rate of Hypoglycemic Events | Baseline through 26 weeks and 52 weeks | Hypoglycemic events (HE) were classified as documented symptomatic hypoglycemia, asymptomatic hypoglycemia, severe hypoglycemia, and probable symptomatic hypoglycemia. The 1-year adjusted rate of HEs was summarized cumulatively at 26 weeks and 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 Self-reported Hypoglycemic Events | Baseline through 26 Weeks and 52 Weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia, and had a plasma glucose level of less than or equal to 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events was 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. |
| Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | Baseline, 26 Weeks, 52 Weeks | Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured. LS means of change from baseline were calculated using a MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate | Baseline, 26 Weeks, 52 Weeks | Seated pulse rate was measured. LS means of change from baseline were calculated using a MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate. |
| Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | Baseline, 26 Weeks, 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. |
| Change From Baseline in HbA1c at 52 Weeks | Baseline, 52 Weeks | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS means of change from baseline in HbA1c were calculated using a MMRM with the change in HbA1c as the dependent variable and treatment, baseline HbA1c, country, OAM, visit, and treatment-by-visit interaction as fixed effects, and participant was as the random effect. |
| Change From Baseline in Pancreatic Enzymes | Baseline, 26 Weeks, 52 Weeks | Amylase (total and pancreas-derived) and lipase concentrations were measured |
| Change From Baseline in Serum Calcitonin | Baseline, 26 Weeks, 52 Weeks | — |
| Number of Participants With Adjudicated Cardiovascular (CV) Events | Baseline through 52 weeks | Deaths and nonfatal cardiovascular adverse events were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular events subjected to adjudication 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 adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Adjudicated Pancreatitis | Baseline through 52 Weeks | The number of participants with pancreatitis confirmed by adjudication is summarized. Events of pancreatitis (including suspected pancreatitis and severe or serious abdominal pain) were adjudicated by a committee of expert physicians external to the Sponsor. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline in Body Weight | Baseline, 26 Weeks, 52 Weeks | — |
| Change in Body Mass Index | Baseline, 26 Weeks, 52 Weeks | Body mass index is an estimate of body fat based on body weight divided by height squared. |
| Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA) | Baseline through 52 Weeks | Number of participants with treatment emergent (TE) dulaglutide anti-drug antibodies from postbaseline to follow up were summarized. A participant was considered to have TE dulaglutide 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. |
| EQ-5D Health State Score Responses | Baseline, 26 Weeks, 52 Weeks | The EQ-5D questionnaire is a widely used, generic questionnaire that assesses health-related quality of life. It consists of 2 parts. The first part 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 3 response categories is summarized for each of the 5 dimensions. |
| Change From Baseline in EQ-5D Visual Analog Scale Score | Baseline, 26 weeks, 52 weeks | The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score was self-reported using a visual analogue scale (VAS) marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. LS means of change from baseline were calculated using ANCOVA and adjusted by treatment, country, and baseline. |
| Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR) | Baseline, 26 Weeks, 52 Weeks | — |
Countries
China, Mexico, Russia, South Korea
Participant flow
Pre-assignment details
This was a parallel-arm, non-inferiority study. Study treatment continued for up to 52 weeks and participants were randomized in a 1:1:1 ratio to one of the 3 treatment arms: 1.5 milligrams (mg) dulaglutide once-weekly , 0.75 mg dulaglutide once-weekly, or insulin glargine once-daily.
Participants by arm
| Arm | Count |
|---|---|
| 1.5 mg Dulaglutide 1.5 mg dulaglutide administered as 1 SC injection once-weekly added to participant's pre-study prescribed dose of metformin and/or a sulfonylurea. | 253 |
| 0.75 mg Dulaglutide 0.75 mg dulaglutide administered as 1 SC injection once-weekly added to participant's pre-study prescribed dose of metformin and/or a sulfonylurea. | 252 |
| Insulin Glargine Insulin glargine administered per dosing titration schedule as once daily SC injection at bedtime added to participant's pre-study prescribed dose of metformin and/or a sulfonylurea. | 250 |
| Total | 755 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 11 | 2 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 9 | 6 | 8 |
| Overall Study | Physician Decision | 0 | 1 | 3 |
| Overall Study | Protocol Violation | 1 | 2 | 1 |
| Overall Study | Sponsor Decision | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 15 | 17 | 17 |
Baseline characteristics
| Characteristic | 0.75 mg Dulaglutide | 1.5 mg Dulaglutide | Insulin Glargine | Total |
|---|---|---|---|---|
| Age, Continuous | 54.54 years STANDARD_DEVIATION 10.006 | 55.03 years STANDARD_DEVIATION 9.572 | 55.44 years STANDARD_DEVIATION 9.197 | 55.00 years STANDARD_DEVIATION 9.593 |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants | 14 Participants | 13 Participants | 41 Participants |
| Race (NIH/OMB) Asian | 209 Participants | 213 Participants | 209 Participants | 631 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 | 29 Participants | 26 Participants | 28 Participants | 83 Participants |
| Region of Enrollment China | 196 Participants | 200 Participants | 195 Participants | 591 Participants |
| Region of Enrollment Korea, Republic of | 13 Participants | 13 Participants | 14 Participants | 40 Participants |
| Region of Enrollment Mexico | 24 Participants | 22 Participants | 24 Participants | 70 Participants |
| Region of Enrollment Russian Federation | 19 Participants | 18 Participants | 17 Participants | 54 Participants |
| Sex: Female, Male Female | 109 Participants | 118 Participants | 111 Participants | 338 Participants |
| Sex: Female, Male Male | 143 Participants | 135 Participants | 139 Participants | 417 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 | 184 / 258 | 188 / 257 | 157 / 253 |
| serious Total, serious adverse events | 24 / 258 | 15 / 257 | 9 / 253 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (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 square (LS) means of change from baseline in HbA1c were calculated using a mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, baseline HbA1c, country, oral antihyperglycemic medication (OAM) , visit, and treatment-by-visit interaction as fixed effects, and participant was the random effect.
Time frame: Baseline, 26 Weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks | -1.73 percentage of HbA1c | Standard Error 0.067 |
| 0.75 mg Dulaglutide | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks | -1.33 percentage of HbA1c | Standard Error 0.067 |
| Insulin Glargine | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks | -1.16 percentage of HbA1c | Standard Error 0.067 |
95% CI: [-0.74, -0.4]
95% CI: [-0.35, -0.01]
Secondary
Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate
Seated pulse rate was measured. LS means of change from baseline were calculated using a MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate | Change From Baseline on Pulse rate at Week 26 | 4.63 beats per minute (bpm) | Standard Error 8.681 |
| 1.5 mg Dulaglutide | Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate | Change From Baseline on Pulse rate at Week 52 | 4.18 beats per minute (bpm) | Standard Error 8.336 |
| 0.75 mg Dulaglutide | Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate | Change From Baseline on Pulse rate at Week 26 | 0.65 beats per minute (bpm) | Standard Error 8.631 |
| 0.75 mg Dulaglutide | Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate | Change From Baseline on Pulse rate at Week 52 | 3.18 beats per minute (bpm) | Standard Error 8.917 |
| Insulin Glargine | Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate | Change From Baseline on Pulse rate at Week 26 | -0.86 beats per minute (bpm) | Standard Error 9.546 |
| Insulin Glargine | Change From Baseline at 26 Weeks and 52 Weeks on Pulse Rate | Change From Baseline on Pulse rate at Week 52 | 0.07 beats per minute (bpm) | Standard Error 8.205 |
Comparison: Week 26p-value: <0.001Mixed Models Analysis
Comparison: Week 52p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks
Participants were required to perform 7-point SMBG profiles on 2 separate, nonconsecutive days during the 2 weeks before randomization and Weeks 8, 14, 20, 26, 39, and 52 (or the Early Discontinuation Visit). SMBG measurements were taken using a plasma-equivalent blood glucose (BG) meter at 7 time points: morning pre-meal, morning 2 hours post-meal, mid-day pre-meal, mid-day 2 hours post-meal, evening pre-meal, evening 2 hours post-meal, and at bedtime. Mean and Week 26 and Week 52 was assessed in all treatment groups. LS means of change from baseline were calculated using MMRM with the change in 7-point SMBG as the dependent variable and treatment, baseline value, country, OAM, visit, and treatment-by-visit interaction as fixed effects, and participant was the random effect.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline.
| 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 and 52 Weeks | Morning pre-meal, Week 26 | -2.18 mmol/L | Standard Error 0.104 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day 2 hours post-meal, Week 52 | -2.75 mmol/L | Standard Error 0.187 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening 2 hours post-meal, Week 26 | -3.00 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 and 52 Weeks | Evening 2 hours post-meal, Week 52 | -2.93 mmol/L | Standard Error 0.183 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day pre-meal, Week 52 | -2.37 mmol/L | Standard Error 0.162 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Bed time, Week 26 | -2.95 mmol/L | Standard Error 0.17 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day pre-meal, Week 26 | -2.45 mmol/L | Standard Error 0.159 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning 2 hours post-meal, Week 52 | -3.58 mmol/L | Standard Error 0.201 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Bed time, Week 52 | -2.90 mmol/L | Standard Error 0.172 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening pre-meal, Week 52 | -2.15 mmol/L | Standard Error 0.159 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day 2 hours post-meal, Week 26 | -3.16 mmol/L | Standard Error 0.182 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning 2 hours post-meal, Week 26 | -3.81 mmol/L | Standard Error 0.19 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning pre-meal, Week 52 | -2.06 mmol/L | Standard Error 0.108 |
| 1.5 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening pre-meal, Week 26 | -2.25 mmol/L | Standard Error 0.15 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day 2 hours post-meal, Week 52 | -2.61 mmol/L | Standard Error 0.186 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning pre-meal, Week 26 | -1.89 mmol/L | Standard Error 0.103 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning 2 hours post-meal, Week 26 | -3.43 mmol/L | Standard Error 0.188 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day pre-meal, Week 26 | -2.07 mmol/L | Standard Error 0.157 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day 2 hours post-meal, Week 26 | -2.71 mmol/L | Standard Error 0.179 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening pre-meal, Week 26 | -1.74 mmol/L | Standard Error 0.147 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening 2 hours post-meal, Week 26 | -2.58 mmol/L | Standard Error 0.178 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Bed time, Week 26 | -2.51 mmol/L | Standard Error 0.167 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning pre-meal, Week 52 | -1.76 mmol/L | Standard Error 0.108 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning 2 hours post-meal, Week 52 | -3.25 mmol/L | Standard Error 0.2 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day pre-meal, Week 52 | -1.89 mmol/L | Standard Error 0.162 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening pre-meal, Week 52 | -1.61 mmol/L | Standard Error 0.158 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening 2 hours post-meal, Week 52 | -2.54 mmol/L | Standard Error 0.182 |
| 0.75 mg Dulaglutide | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Bed time, Week 52 | -2.50 mmol/L | Standard Error 0.171 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening 2 hours post-meal, Week 52 | -2.10 mmol/L | Standard Error 0.18 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day pre-meal, Week 52 | -1.94 mmol/L | Standard Error 0.16 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening pre-meal, Week 26 | -1.62 mmol/L | Standard Error 0.148 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day 2 hours post-meal, Week 26 | -2.11 mmol/L | Standard Error 0.179 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day 2 hours post-meal, Week 52 | -2.12 mmol/L | Standard Error 0.184 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Mid-day pre-meal, Week 26 | -2.10 mmol/L | Standard Error 0.157 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning pre-meal, Week 26 | -2.83 mmol/L | Standard Error 0.103 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening pre-meal, Week 52 | -1.51 mmol/L | Standard Error 0.156 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning 2 hours post-meal, Week 26 | -3.32 mmol/L | Standard Error 0.188 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning pre-meal, Week 52 | -2.83 mmol/L | Standard Error 0.107 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Bed time, Week 26 | -2.16 mmol/L | Standard Error 0.167 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Bed time, Week 52 | -1.91 mmol/L | Standard Error 0.168 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Morning 2 hours post-meal, Week 52 | -3.05 mmol/L | Standard Error 0.197 |
| Insulin Glargine | Change From Baseline in 7-point Self-monitored Blood Glucose (SMBG) Profiles at 26 Weeks and 52 Weeks | Evening 2 hours post-meal, Week 26 | -2.11 mmol/L | Standard Error 0.178 |
Comparison: Morning pre-meal, Week 26p-value: <0.00195% CI: [0.42, 0.88]Mixed Models Analysis
Comparison: Morning pre-meal, Week 26p-value: <0.00195% CI: [0.71, 1.17]Mixed Models Analysis
Comparison: Morning 2-hours post-meal, Week 26p-value: 0.02495% CI: [-0.92, -0.07]Mixed Models Analysis
Comparison: Morning 2-hours post-meal, Week 26p-value: 0.61795% CI: [-0.53, 0.32]Mixed Models Analysis
Comparison: Mid-day pre-meal, Week 26p-value: 0.05595% CI: [-0.7, 0.01]Mixed Models Analysis
Comparison: Mid-day pre-meal, Week 26p-value: 0.85595% CI: [-0.32, 0.39]Mixed Models Analysis
Comparison: Mid-day 2-hours post-meal, Week 26p-value: <0.00195% CI: [-1.46, -0.64]Mixed Models Analysis
Comparison: Mid-day 2-hours post-meal, Week 26p-value: 0.00495% CI: [-1.01, -0.19]Mixed Models Analysis
Comparison: Evening pre-meal, Week 26p-value: <0.00195% CI: [-0.97, -0.29]Mixed Models Analysis
Comparison: Evening pre-meal, Week 26p-value: 0.48995% CI: [-0.45, 0.22]Mixed Models Analysis
Comparison: Evening 2-hours post-meal, Week 26p-value: <0.00195% CI: [-1.3, -0.48]Mixed Models Analysis
Comparison: Evening 2-hours post-meal, Week 26p-value: 0.02495% CI: [-0.88, -0.06]Mixed Models Analysis
Comparison: Bedtime, Week 26p-value: <0.00195% CI: [-1.17, -0.41]Mixed Models Analysis
Comparison: Bedtime, Week 26p-value: 0.06795% CI: [-0.73, -0.03]Mixed Models Analysis
Comparison: Morning pre-meal, Week 52p-value: <0.00195% CI: [0.52, 1.01]Mixed Models Analysis
Comparison: Morning pre-meal, Week 52p-value: <0.00195% CI: [0.82, 1.31]Mixed Models Analysis
Comparison: Morning 2-hours post-meal, Week 52p-value: 0.02595% CI: [-1, -0.07]Mixed Models Analysis
Comparison: Morning 2-hours post-meal, Week 52p-value: 0.38495% CI: [-0.67, 0.26]Mixed Models Analysis
Comparison: Mid-day pre-meal, Week 52p-value: 0.02495% CI: [-0.8, -0.06]Mixed Models Analysis
Comparison: Mid-day pre-meal, Week 52p-value: 0.78395% CI: [-0.32, 0.42]Mixed Models Analysis
Comparison: Mid-day 2-hours post-meal, Week 52p-value: 0.00495% CI: [-1.07, -0.2]Mixed Models Analysis
Comparison: Mid-day 2-hours post-meal, Week 52p-value: 0.02995% CI: [-0.92, -0.05]Mixed Models Analysis
Comparison: Evening pre-meal, Week 52p-value: <0.00195% CI: [-1.01, -0.27]Mixed Models Analysis
Comparison: Evening pre-meal, Week 52p-value: 0.60395% CI: [-0.47, 0.27]Mixed Models Analysis
Comparison: Evening 2-hours post-meal, Week 52p-value: <0.00195% CI: [-1.26, -0.41]Mixed Models Analysis
Comparison: Evening 2-hours post-meal, Week 52p-value: 0.03995% CI: [-0.87, -0.02]Mixed Models Analysis
Comparison: Bedtime, Week 52p-value: <0.00195% CI: [-1.39, -0.6]Mixed Models Analysis
Comparison: Bedtime, Week 52p-value: 0.00395% CI: [-0.98, -0.2]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Body Weight | Week 52 | -1.08 kilogram (kg) | Standard Error 0.201 |
| 1.5 mg Dulaglutide | Change From Baseline in Body Weight | Week 26 | -1.47 kilogram (kg) | Standard Error 0.197 |
| 0.75 mg Dulaglutide | Change From Baseline in Body Weight | Week 26 | -0.88 kilogram (kg) | Standard Error 0.197 |
| 0.75 mg Dulaglutide | Change From Baseline in Body Weight | Week 52 | -0.76 kilogram (kg) | Standard Error 0.202 |
| Insulin Glargine | Change From Baseline in Body Weight | Week 26 | 0.97 kilogram (kg) | Standard Error 0.198 |
| Insulin Glargine | Change From Baseline in Body Weight | Week 52 | 1.35 kilogram (kg) | Standard Error 0.201 |
p-value: <0.001Mixed Models Analysis
Comparison: Week 52p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline 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.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval 26 Weeks | -1.65 millisecond (msec) | Standard Deviation 13.157 |
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval 26 Weeks | 3.09 millisecond (msec) | Standard Deviation 1.7 |
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval 52 Weeks | 0.55 millisecond (msec) | Standard Deviation 11.209 |
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval 52 Weeks | 3.60 millisecond (msec) | Standard Deviation 12.425 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval 52 Weeks | 3.55 millisecond (msec) | Standard Deviation 11.526 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval 26 Weeks | 0.76 millisecond (msec) | Standard Deviation 11.643 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval 52 Weeks | 1.19 millisecond (msec) | Standard Deviation 12.165 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval 26 Weeks | 2.88 millisecond (msec) | Standard Deviation 10.801 |
| Insulin Glargine | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval 52 Weeks | 0.63 millisecond (msec) | Standard Deviation 11.861 |
| Insulin Glargine | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | PR Interval 26 Weeks | -0.86 millisecond (msec) | Standard Deviation 10.272 |
| Insulin Glargine | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval 52 Weeks | 4.03 millisecond (msec) | Standard Deviation 11.446 |
| Insulin Glargine | Change From Baseline in Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval | QTcF Interval 26 Weeks | 2.56 millisecond (msec) | Standard Deviation 11.911 |
Secondary
Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR)
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR) | Week 26 | 6.13 beats per minute (bpm) | Standard Deviation 8.924 |
| 1.5 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR) | Week 52 | 5.04 beats per minute (bpm) | Standard Deviation 8.223 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR) | Week 26 | 3.77 beats per minute (bpm) | Standard Deviation 9.002 |
| 0.75 mg Dulaglutide | Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR) | Week 52 | 3.40 beats per minute (bpm) | Standard Deviation 7.986 |
| Insulin Glargine | Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR) | Week 26 | -0.46 beats per minute (bpm) | Standard Deviation 9.329 |
| Insulin Glargine | Change From Baseline in Electrocardiogram Parameters, Heart Rate (HR) | Week 52 | 0.43 beats per minute (bpm) | Standard Deviation 8.06 |
Secondary
Change From Baseline in EQ-5D Visual Analog Scale Score
The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score was self-reported using a visual analogue scale (VAS) marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state. LS means of change from baseline were calculated using ANCOVA and adjusted by treatment, country, and baseline.
Time frame: Baseline, 26 weeks, 52 weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in EQ-5D Visual Analog Scale Score | Week 26 | 1.08 units on a scale | Standard Deviation 12.644 |
| 1.5 mg Dulaglutide | Change From Baseline in EQ-5D Visual Analog Scale Score | Week 52 | 2.65 units on a scale | Standard Deviation 12.029 |
| 0.75 mg Dulaglutide | Change From Baseline in EQ-5D Visual Analog Scale Score | Week 26 | 1.67 units on a scale | Standard Deviation 13.456 |
| 0.75 mg Dulaglutide | Change From Baseline in EQ-5D Visual Analog Scale Score | Week 52 | 2.34 units on a scale | Standard Deviation 14.003 |
| Insulin Glargine | Change From Baseline in EQ-5D Visual Analog Scale Score | Week 26 | 1.41 units on a scale | Standard Deviation 10.885 |
| Insulin Glargine | Change From Baseline in EQ-5D Visual Analog Scale Score | Week 52 | 2.55 units on a scale | Standard Deviation 12.257 |
Secondary
Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks
LS means of change from baseline were calculated using MMRM with the change in FBG as the dependent variable and treatment, baseline value, country, OAM, visit, and treatment-by-visit interaction as fixed effects, and participant was the random effect.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks | Change from baseline in FBG, 26 Weeks | -2.35 millimoles per liter (mmol/L) | Standard Error 0.162 |
| 1.5 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks | Change from baseline in FBG, 52 Weeks | -2.23 millimoles per liter (mmol/L) | Standard Error 0.166 |
| 0.75 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks | Change from baseline in FBG, 26 Weeks | -1.71 millimoles per liter (mmol/L) | Standard Error 0.161 |
| 0.75 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks | Change from baseline in FBG, 52 Weeks | -1.53 millimoles per liter (mmol/L) | Standard Error 0.165 |
| Insulin Glargine | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks | Change from baseline in FBG, 26 Weeks | -2.59 millimoles per liter (mmol/L) | Standard Error 0.161 |
| Insulin Glargine | Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks | Change from baseline in FBG, 52 Weeks | -2.35 millimoles per liter (mmol/L) | Standard Error 0.164 |
Comparison: Week 26p-value: 0.17795% CI: [-0.11, 0.59]Mixed Models Analysis
Comparison: Week 26p-value: <0.00195% CI: [0.53, 1.23]Mixed Models Analysis
Comparison: Week 52p-value: 0.51895% CI: [-0.25, 0.5]Mixed Models Analysis
Comparison: Week 52p-value: <0.00195% CI: [0.45, 1.2]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c at 52 Weeks
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS means of change from baseline in HbA1c were calculated using a MMRM with the change in HbA1c as the dependent variable and treatment, baseline HbA1c, country, OAM, visit, and treatment-by-visit interaction as fixed effects, and participant was as the random effect.
Time frame: Baseline, 52 Weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in HbA1c at 52 Weeks | -1.47 percentage of HbA1c | Standard Error 0.076 |
| 0.75 mg Dulaglutide | Change From Baseline in HbA1c at 52 Weeks | -1.03 percentage of HbA1c | Standard Error 0.076 |
| Insulin Glargine | Change From Baseline in HbA1c at 52 Weeks | -0.89 percentage of HbA1c | Standard Error 0.075 |
95% CI: [-0.77, -0.38]
95% CI: [-0.33, -0.06]
Secondary
Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks and 52 Weeks
The HOMA2 was used to estimate the steady-state insulin sensitivity (%S). HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as a percentage of the normal reference population. LS means were calculated using an homeostasis model assessment with change from baseline in HOMA-%S as a covariate and country, baseline measurement, OAM, and treatment as fixed effects.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method. HOMA2 was not evaluated for insulin glargine, as the use of this model has not been validated in participants treated with insulin.
| 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 and 52 Weeks | Insulin-Based HOMA2-%S, Week 26 | -6.86 percentage of HOMA2-%S | Standard Error 3.649 |
| 1.5 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks and 52 Weeks | Insulin-Based HOMA2-%S, Week 52 | -10.19 percentage of HOMA2-%S | Standard Error 3.677 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks and 52 Weeks | Insulin-Based HOMA2-%S, Week 26 | -10.03 percentage of HOMA2-%S | Standard Error 3.591 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Insulin Sensitivity - Cell Function (HOMA2-%S) at 26 Weeks and 52 Weeks | Insulin-Based HOMA2-%S, Week 52 | -12.32 percentage of HOMA2-%S | Standard Error 3.609 |
Comparison: HOMA2-%S, Dula 1.5 mg, Week 26p-value: 0.025Mixed Models Analysis
Comparison: HOMA2-%S, Dula 0.75 mg, Week 26p-value: 0.025Mixed Models Analysis
Comparison: HOMA2-%S, Dula 1.5 mg, Week 52p-value: 0.029Mixed Models Analysis
Comparison: HOMA2-%S, Dula 0.75 mg, Week 52p-value: 0.029Mixed Models Analysis
Secondary
Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weeks
The updated Homeostasis Model Assessment (HOMA2) was used to quantify steady state beta-cell function (%B). HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate %B as a percentage of a normal reference population. LS means were calculated using a homeostasis model assessment with change from baseline in HOMA-%B as a covariate and country, baseline measurement, OAM, and treatment as fixed effects.
Time frame: Baseline, 26 weeks, 52 weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method. HOMA2 was not evaluated for insulin glargine, as the use of this model has not been validated in participants treated with insulin.
| 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 and 52 Weeks | Insulin-Based HOMA2-%B, 26 Weeks | 34.41 percentage of HOMA2-%B | Standard Error 3.831 |
| 1.5 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weeks | Insulin-Based HOMA2-%B, 52 Weeks | 45.12 percentage of HOMA2-%B | Standard Error 4.147 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weeks | Insulin-Based HOMA2-%B, 26 Weeks | 31.17 percentage of HOMA2-%B | Standard Error 3.761 |
| 0.75 mg Dulaglutide | Change From Baseline in Homeostasis Model Assessment 2 Steady-state Beta (β)- Cell Function (HOMA2-%B) at 26 Weeks and 52 Weeks | Insulin-Based HOMA2-%B, 52 Weeks | 36.64 percentage of HOMA2-%B | Standard Error 4.061 |
Comparison: HOMA2-%B, Dula 1.5 mg, Week 26p-value: 0.352Mixed Models Analysis
Comparison: HOMA2-%B, Dula 0.75 mg, Week 26p-value: 0.352Mixed Models Analysis
Comparison: HOMA2-%B, Dula 1.5, Week 52p-value: 0.025Mixed Models Analysis
Comparison: HOMA2-%B, Dula 0.75 mg, Week 52p-value: 0.025Mixed Models Analysis
Secondary
Change From Baseline in Pancreatic Enzymes
Amylase (total and pancreas-derived) and lipase concentrations were measured
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, Total 26 Weeks | 7.50 Units/Liter (U/L) | Standard Deviation 18.755 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, Total 52 Weeks | 7.82 Units/Liter (U/L) | Standard Deviation 16.25 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Lipase 26 Weeks | 11.00 Units/Liter (U/L) | Standard Deviation 34.134 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Lipase 52 Weeks | 10.76 Units/Liter (U/L) | Standard Deviation 27.36 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, pancreas derived 52 Weeks | 5.48 Units/Liter (U/L) | Standard Deviation 12.449 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, pancreas derived 26 Weeks | 5.83 Units/Liter (U/L) | Standard Deviation 14.607 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Lipase 26 Weeks | 10.67 Units/Liter (U/L) | Standard Deviation 39.989 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, Total 26 Weeks | 7.54 Units/Liter (U/L) | Standard Deviation 22.388 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, pancreas derived 26 Weeks | 5.14 Units/Liter (U/L) | Standard Deviation 19.36 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Lipase 52 Weeks | 9.64 Units/Liter (U/L) | Standard Deviation 33.715 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, Total 52 Weeks | 6.42 Units/Liter (U/L) | Standard Deviation 20.675 |
| 0.75 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes | Amylase, pancreas derived 52 Weeks | 4.05 Units/Liter (U/L) | Standard Deviation 15.49 |
| Insulin Glargine | Change From Baseline in Pancreatic Enzymes | Amylase, pancreas derived 52 Weeks | -0.49 Units/Liter (U/L) | Standard Deviation 12.576 |
| Insulin Glargine | Change From Baseline in Pancreatic Enzymes | Amylase, Total 52 Weeks | 0.64 Units/Liter (U/L) | Standard Deviation 18.696 |
| Insulin Glargine | Change From Baseline in Pancreatic Enzymes | Amylase, Total 26 Weeks | -0.37 Units/Liter (U/L) | Standard Deviation 18.196 |
| Insulin Glargine | Change From Baseline in Pancreatic Enzymes | Lipase 52 Weeks | -3.66 Units/Liter (U/L) | Standard Deviation 20.484 |
| Insulin Glargine | Change From Baseline in Pancreatic Enzymes | Lipase 26 Weeks | -2.74 Units/Liter (U/L) | Standard Deviation 21.818 |
| Insulin Glargine | Change From Baseline in Pancreatic Enzymes | Amylase, pancreas derived 26 Weeks | -0.21 Units/Liter (U/L) | Standard Deviation 11.287 |
Secondary
Change From Baseline in Serum Calcitonin
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline in Serum Calcitonin | Week 26 | 0.01 picomole/liter | Standard Deviation 0.24 |
| 1.5 mg Dulaglutide | Change From Baseline in Serum Calcitonin | Week 52 | -0.03 picomole/liter | Standard Deviation 0.279 |
| 0.75 mg Dulaglutide | Change From Baseline in Serum Calcitonin | Week 26 | -0.07 picomole/liter | Standard Deviation 0.289 |
| 0.75 mg Dulaglutide | Change From Baseline in Serum Calcitonin | Week 52 | -0.08 picomole/liter | Standard Deviation 0.325 |
| Insulin Glargine | Change From Baseline in Serum Calcitonin | Week 26 | 0.02 picomole/liter | Standard Deviation 0.256 |
| Insulin Glargine | Change From Baseline in Serum Calcitonin | Week 52 | -0.05 picomole/liter | Standard Deviation 0.306 |
Secondary
Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP)
Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured. LS means of change from baseline were calculated using a MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects and baseline as a covariate.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | SBP 26 Weeks | -5.53 millimeters of mercury (mmHg)] | Standard Error 12.037 |
| 1.5 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | DBP 26 Weeks | -1.58 millimeters of mercury (mmHg)] | Standard Error 7.842 |
| 1.5 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | SBP 52 Weeks | -2.18 millimeters of mercury (mmHg)] | Standard Error 11.134 |
| 1.5 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | DBP 52 Weeks | -0.19 millimeters of mercury (mmHg)] | Standard Error 7.542 |
| 0.75 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | DBP 52 Weeks | 0.44 millimeters of mercury (mmHg)] | Standard Error 7.582 |
| 0.75 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | SBP 26 Weeks | -2.77 millimeters of mercury (mmHg)] | Standard Error 11.92 |
| 0.75 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | SBP 52 Weeks | -0.61 millimeters of mercury (mmHg)] | Standard Error 12.081 |
| 0.75 mg Dulaglutide | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | DBP 26 Weeks | -0.92 millimeters of mercury (mmHg)] | Standard Error 7.898 |
| Insulin Glargine | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | DBP 52 Weeks | -1.13 millimeters of mercury (mmHg)] | Standard Error 8.81 |
| Insulin Glargine | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | DBP 26 Weeks | -1.61 millimeters of mercury (mmHg)] | Standard Error 8.417 |
| Insulin Glargine | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | SBP 52 Weeks | -0.25 millimeters of mercury (mmHg)] | Standard Error 11.717 |
| Insulin Glargine | Change From Baseline to 26 Weeks and 52 Weeks on Blood Pressure (BP) | SBP 26 Weeks | -2.22 millimeters of mercury (mmHg)] | Standard Error 12.743 |
Comparison: Week 26 SBPp-value: 0.008Mixed Models Analysis
Comparison: Week 26 DBPp-value: 0.584Mixed Models Analysis
Comparison: Week 52 SBPp-value: 0.169Mixed Models Analysis
Comparison: Week 52 DBPp-value: 0.11Mixed Models Analysis
Secondary
Change in Body Mass Index
Body mass index is an estimate of body fat based on body weight divided by height squared.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Change in Body Mass Index | Week 26 | -0.53 kilogram/square meter (kg/m2) | Standard Error 0.071 |
| 1.5 mg Dulaglutide | Change in Body Mass Index | Week 52 | -0.40 kilogram/square meter (kg/m2) | Standard Error 0.072 |
| 0.75 mg Dulaglutide | Change in Body Mass Index | Week 26 | -0.32 kilogram/square meter (kg/m2) | Standard Error 0.071 |
| 0.75 mg Dulaglutide | Change in Body Mass Index | Week 52 | -0.27 kilogram/square meter (kg/m2) | Standard Error 0.072 |
| Insulin Glargine | Change in Body Mass Index | Week 26 | 0.37 kilogram/square meter (kg/m2) | Standard Error 0.071 |
| Insulin Glargine | Change in Body Mass Index | Week 52 | 0.52 kilogram/square meter (kg/m2) | Standard Error 0.072 |
Comparison: Week 26p-value: <0.001Mixed Models Analysis
Comparison: Week 52p-value: <0.001Mixed Models Analysis
Secondary
EQ-5D Health State Score Responses
The EQ-5D questionnaire is a widely used, generic questionnaire that assesses health-related quality of life. It consists of 2 parts. The first part 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 3 response categories is summarized for each of the 5 dimensions.
Time frame: Baseline, 26 Weeks, 52 Weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - extreme problems Week 26 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - some problem Week 26 | 7 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - extreme problem Week 26 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - missing Week 26 | 4 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - no problem Week 26 | 223 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - some problem Week 26 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - extreme problem Week 26 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - missing Week 26 | 4 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - no problems Week 26 | 219 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - some problems Week 26 | 7 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - no problem Week 26 | 219 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - missing Week 26 | 4 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - no problems Week 26 | 193 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - some problems Week 26 | 32 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - ambiguous | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - missing Week 26 | 4 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - no problems Week 26 | 208 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - some problems Week 26 | 19 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - extreme problems Week 26 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - missing Week 26 | 4 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - no problems Week 52 | 218 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - some problems Week 52 | 8 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - extreme problems Week 52 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - missing Week 52 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - no problems Week 52 | 224 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - some problems Week 52 | 2 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - extreme problems Week 52 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - missing Week 52 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - no problems Week 52 | 219 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - some problems Week 52 | 6 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - extreme problems Week 52 | 1 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - missing Week 52 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - no problems Week 52 | 191 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - some problems Week 52 | 34 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - extreme problems Week 52 | 1 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - missing Week 52 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - no problems Week 52 | 205 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - some problems Week 52 | 21 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - extreme problems Week 52 | 0 participants |
| 1.5 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - missing Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - no problems Week 52 | 207 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - no problem Week 26 | 215 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - missing Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - missing Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - some problem Week 26 | 16 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - some problems Week 52 | 33 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - missing Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - extreme problem Week 26 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - some problems Week 52 | 14 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - no problems Week 52 | 188 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - missing Week 26 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - extreme problems Week 26 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - extreme problems Week 52 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - no problem Week 26 | 227 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - no problems Week 26 | 204 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - no problems Week 52 | 211 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - some problem Week 26 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - missing Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Mobility - missing Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - extreme problem Week 26 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - missing Week 26 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - extreme problems Week 52 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - missing Week 26 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - no problems Week 52 | 215 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - some problems Week 52 | 10 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - no problems Week 26 | 220 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - missing Week 26 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - ambiguous | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - some problems Week 26 | 11 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - some problems Week 52 | 7 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - no problems Week 52 | 207 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - extreme problems Week 26 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - some problems Week 26 | 27 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual Activities - extreme problems Week 52 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Usual activities - missing Week 26 | 1 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - extreme problems Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Anxiety/Depression - some problems Week 52 | 15 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - no problems Week 26 | 201 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Self-care - extreme problems Week 52 | 0 participants |
| 0.75 mg Dulaglutide | EQ-5D Health State Score Responses | Pain/Discomfort - some problems Week 26 | 30 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual Activities - extreme problems Week 52 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - some problems Week 26 | 37 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - no problems Week 52 | 201 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - ambiguous | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - missing Week 26 | 4 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual Activities - missing Week 52 | 1 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - no problems Week 26 | 203 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - missing Week 52 | 1 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - some problems Week 26 | 26 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - extreme problems Week 26 | 1 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - no problems Week 52 | 185 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - missing Week 26 | 4 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - some problems Week 52 | 29 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - no problems Week 52 | 214 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - some problems Week 52 | 16 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - some problems Week 52 | 43 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - extreme problems Week 52 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - missing Week 52 | 1 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - no problems Week 52 | 223 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - extreme problems Week 52 | 1 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - some problems Week 52 | 7 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - extreme problems Week 52 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - no problem Week 26 | 210 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - some problem Week 26 | 20 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - extreme problem Week 26 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - missing Week 52 | 1 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Mobility - missing Week 26 | 4 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - missing Week 52 | 1 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - no problem Week 26 | 224 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - some problem Week 26 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual Activities - no problems Week 52 | 219 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - extreme problem Week 26 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Anxiety/Depression - extreme problems Week 52 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Self-care - missing Week 26 | 4 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual activities - no problems Week 26 | 218 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual Activities - some problems Week 52 | 11 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual activities - some problems Week 26 | 11 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual activities - extreme problems Week 26 | 0 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Usual activities - missing Week 26 | 4 participants |
| Insulin Glargine | EQ-5D Health State Score Responses | Pain/Discomfort - no problems Week 26 | 188 participants |
Secondary
Number of Participants With Adjudicated Cardiovascular (CV) Events
Deaths and nonfatal cardiovascular adverse events were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular events subjected to adjudication 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 adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 52 weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg Dulaglutide | Number of Participants With Adjudicated Cardiovascular (CV) Events | 6 participants with adjudicated CV events |
| 0.75 mg Dulaglutide | Number of Participants With Adjudicated Cardiovascular (CV) Events | 2 participants with adjudicated CV events |
| Insulin Glargine | Number of Participants With Adjudicated Cardiovascular (CV) Events | 2 participants with adjudicated CV events |
Secondary
Number of Participants With Adjudicated Pancreatitis
The number of participants with pancreatitis confirmed by adjudication is summarized. Events of pancreatitis (including suspected pancreatitis and severe or serious abdominal pain) were adjudicated by a committee of expert physicians external to the Sponsor. 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 in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1.5 mg Dulaglutide | Number of Participants With Adjudicated Pancreatitis | 0 participants |
| 0.75 mg Dulaglutide | Number of Participants With Adjudicated Pancreatitis | 0 participants |
| Insulin Glargine | Number of Participants With Adjudicated Pancreatitis | 0 participants |
Secondary
Number of Self-reported Hypoglycemic Events
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia, and had a plasma glucose level of less than or equal to 3.9 millimoles/liter \[mmol/L\]), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of less than or equal to 3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). The number of self-reported hypoglycemic events was 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 26 Weeks and 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Probable HE Week 52 | 4.7 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Documented Symptomatic HE Week 52 | 12.4 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Total HE Week 52 | 22.5 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Asymptomatic HE Week 26 | 10.1 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Severe HE Week 26 | 0.0 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Probable HE Week 26 | 4.3 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Total HE Week 26 | 19.4 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Nocturnal HE Week 52 | 7.0 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Nocturnal HE Week 26 | 6.2 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Asymptomatic HE Week 52 | 12.0 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Severe HE Week 52 | 0.0 percentage of participants |
| 1.5 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Documented Symptomatic Week 26 | 11.2 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Asymptomatic HE Week 52 | 10.1 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Total HE Week 26 | 16.7 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Severe HE Week 26 | 0.0 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Nocturnal HE Week 26 | 3.9 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Documented Symptomatic Week 26 | 7.8 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Asymptomatic HE Week 26 | 8.2 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Probable HE Week 26 | 5.1 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Total HE Week 52 | 19.8 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Severe HE Week 52 | 0.0 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Nocturnal HE Week 52 | 4.3 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Probable HE Week 52 | 5.4 percentage of participants |
| 0.75 mg Dulaglutide | Number of Self-reported Hypoglycemic Events | Documented Symptomatic HE Week 52 | 9.7 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Nocturnal HE Week 26 | 11.1 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Probable HE Week 52 | 8.3 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Severe HE Week 52 | 0.0 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Severe HE Week 26 | 0.0 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Documented Symptomatic HE Week 52 | 20.6 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Asymptomatic HE Week 52 | 19.4 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Asymptomatic HE Week 26 | 14.2 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Nocturnal HE Week 52 | 13.8 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Probable HE Week 26 | 7.5 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Documented Symptomatic Week 26 | 17.0 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Total HE Week 26 | 29.6 percentage of participants |
| Insulin Glargine | Number of Self-reported Hypoglycemic Events | Total HE Week 52 | 34.8 percentage of participants |
Secondary
Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks
The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
Time frame: Up to 26 and 52 weeks
Population: Participants who were randomized, received at least one dose of study drug, and had evaluable HbA1c data at both baseline and post-baseline. Missing endpoints were imputed with the last observation carried forward (LOCF) method.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c <7%, Week 26 | 64.8 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c ≤6.5%, Week 26 | 51.4 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c <7%, Week 52 | 51.8 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c ≤6.5%, Week 52 | 37.2 percentage of participants |
| 0.75 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c ≤6.5%, Week 52 | 31.3 percentage of participants |
| 0.75 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c <7%, Week 26 | 52.8 percentage of participants |
| 0.75 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c <7%, Week 52 | 45.6 percentage of participants |
| 0.75 mg Dulaglutide | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c ≤6.5%, Week 26 | 38.9 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c ≤6.5%, Week 52 | 17.2 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c ≤6.5%, Week 26 | 21.6 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c <7%, Week 52 | 32.0 percentage of participants |
| Insulin Glargine | Percentage of Participants Attaining HbA1c of <7% or ≤6.5% at 26 Weeks and 52 Weeks | HbA1c <7%, Week 26 | 40.0 percentage of participants |
Comparison: \<7.0% Week 26p-value: <0.001Fisher Exact
Comparison: \<7.0 Week 26p-value: 0.004Fisher Exact
Comparison: \<=6.5% Week 26p-value: <0.001Fisher Exact
Comparison: \<=6.5% Week 26p-value: <0.001Fisher Exact
Comparison: \<7.0% Week 52p-value: <0.001Fisher Exact
Comparison: \<7.0% Week 52p-value: 0.002Fisher Exact
Comparison: \<=6.5% Week 52p-value: <0.001Fisher Exact
Comparison: \<=6.5% Week 52p-value: <0.001Fisher Exact
Secondary
Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA)
Number of participants with treatment emergent (TE) dulaglutide anti-drug antibodies from postbaseline to follow up were summarized. A participant was considered to have TE dulaglutide ADA if the participant had at least one titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.
Time frame: Baseline through 52 Weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1.5 mg Dulaglutide | Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA) | Participants with >=1 TE Dula ADA | 3.9 Percentage of participants |
| 1.5 mg Dulaglutide | Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA) | Participants with TE Dula ADA and Neutralizing | 0.8 Percentage of participants |
| 0.75 mg Dulaglutide | Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA) | Participants with >=1 TE Dula ADA | 4.3 Percentage of participants |
| 0.75 mg Dulaglutide | Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA) | Participants with TE Dula ADA and Neutralizing | 1.6 Percentage of participants |
| Insulin Glargine | Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA) | Participants with >=1 TE Dula ADA | 1.6 Percentage of participants |
| Insulin Glargine | Percentages of Participants Developing Treatment-Emergent Dulaglutide Anti-drug Antibody (ADA) | Participants with TE Dula ADA and Neutralizing | 0.0 Percentage of participants |
Secondary
Rate of Hypoglycemic Events
Hypoglycemic events (HE) were classified as documented symptomatic hypoglycemia, asymptomatic hypoglycemia, severe hypoglycemia, and probable symptomatic hypoglycemia. The 1-year adjusted rate of HEs was summarized cumulatively at 26 weeks 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: Baseline through 26 weeks and 52 weeks
Population: Participants in the safety population who were randomized and received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Events | Nocturnal HE Week 26 | 0.19 events per participant per year | Standard Deviation 0.904 |
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Events | 1-year Rate of HE, Week 26 | 1.27 events per participant per year | Standard Deviation 4.485 |
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Events | Severe HE Week 26 | NA events per participant per year | — |
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Events | 1-year Rate of HE, Week 52 | 0.89 events per participant per year | Standard Deviation 3.777 |
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Events | Severe HE Week 52 | NA events per participant per year | — |
| 1.5 mg Dulaglutide | Rate of Hypoglycemic Events | Nocturnal HE Week 52 | 0.11 events per participant per year | Standard Deviation 0.488 |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Events | Severe HE Week 26 | NA events per participant per year | — |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Events | Nocturnal HE Week 26 | 0.13 events per participant per year | Standard Deviation 0.762 |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Events | 1-year Rate of HE, Week 52 | 0.80 events per participant per year | Standard Deviation 3.914 |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Events | Nocturnal HE Week 52 | 0.10 events per participant per year | Standard Deviation 0.551 |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Events | Severe HE Week 52 | NA events per participant per year | — |
| 0.75 mg Dulaglutide | Rate of Hypoglycemic Events | 1-year Rate of HE, Week 26 | 0.98 events per participant per year | Standard Deviation 4.202 |
| Insulin Glargine | Rate of Hypoglycemic Events | 1-year Rate of HE, Week 26 | 2.13 events per participant per year | Standard Deviation 6.724 |
| Insulin Glargine | Rate of Hypoglycemic Events | Severe HE Week 52 | NA events per participant per year | — |
| Insulin Glargine | Rate of Hypoglycemic Events | Nocturnal HE Week 26 | 0.38 events per participant per year | Standard Deviation 1.444 |
| Insulin Glargine | Rate of Hypoglycemic Events | Nocturnal HE Week 52 | 0.31 events per participant per year | Standard Deviation 1.261 |
| Insulin Glargine | Rate of Hypoglycemic Events | Severe HE Week 26 | NA events per participant per year | — |
| Insulin Glargine | Rate of Hypoglycemic Events | 1-year Rate of HE, Week 52 | 1.92 events per participant per year | Standard Deviation 6.983 |