Diabetes Mellitus, Diabetes Mellitus, Type 2, Endocrine System Diseases, Glucose Metabolism Disorders, Hypoglycemic Agents, Metabolic Disease, Type 2 Diabetes Mellitus (T2DM)
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of 2 doses of dulaglutide in Japanese participants with type 2 diabetes. The study duration is approximately 58 weeks.
Interventions
DRUGDulaglutide
Administered SC
DRUGOral antihyperglycemics
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with type 2 diabetes (T2D) ≥ 6 months according to the World Health Organization (WHO) classification. * Treated with stable doses of a single OAM for at least 8 weeks prior to screening; the dose must be more than or equal to minimum maintenance dose. * Have the following HbA1c result at screening. * Participants taking DPP-4i: ≥7.5% and ≤9.5%, * Participants taking another OAM: ≥8.0% and ≤10.0% * Stable body weight for at least 8 weeks prior to screening or not changed by more than 5 % in the past 8 weeks * Have a body mass index (BMI) ≥18.5 kilogram/square meter (kg/m²) and \<35 kg/m² at Day 1.
Exclusion criteria
* Have type 1 diabetes (T1D) * Have a history of ≥1 episode of ketoacidosis or hyperosmolar state/coma * Have had any myocardial infarction (MI), heart failure or cerebrovascular accident (stroke) * Have a known clinically significant gastric empty abnormality * Have acute or chronic hepatitis * Have had chronic or acute pancreatitis * Have any self or family history of type 2A or type 2B multiple endocrine neoplasia in the absence of known C-cell hyperplasia * Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial, or part of Multiple endocrine neoplasia (MEN) 2A or 2B syndrome) * Have evidence of significant, active autoimmune abnormality * Have evidence of significant, uncontrolled endocrine abnormality * Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years * Have any hematologic condition that may interfere with HbA1c measurement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | Baseline, Week 26 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Pre-study oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment × Time as variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c at Week 52 | Baseline, Week 52 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables. |
| Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% | Week 52 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The odds ratios, confidence intervals, and p-values were determined by generalized linear mixed model (GLM) with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables. |
| Change From Baseline in Fasting Serum Glucose (FSG) | Baseline, Week 52 | FSG is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment\*Time as variables. |
| Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Baseline, Week 26 | SMBG 6-point profiles were measured at morning (premeal-fasting, 2-hour post meal), midday (premeal, 2-hour post meal), and evening (premeal, 2-hour post meal). LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment as variables. |
| Change From Baseline in Body Weight | Baseline, Week 52 | LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment\*Time as variables. |
Countries
Japan
Participant flow
Recruitment details
591 participants were randomized in the study. However, due to good clinical practice (GCP) compliance issues identified at one of the investigative sites, all 5 participants from that site were excluded from the study analyses.
Participants by arm
| Arm | Count |
|---|---|
| Dulaglutide 1.5 mg Participants received 1.5 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide. | 391 |
| Dulaglutide 0.75 mg Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide. | 195 |
| Total | 586 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Due to long-term overseas business trips | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 9 | 5 |
Baseline characteristics
| Characteristic | Dulaglutide 1.5 mg | Dulaglutide 0.75 mg | Total |
|---|---|---|---|
| Age, Continuous | 60.10 years STANDARD_DEVIATION 10.7 | 60.70 years STANDARD_DEVIATION 10.74 | 60.30 years STANDARD_DEVIATION 10.71 |
| Hemoglobin A1c (HbA1c) | 8.61 Percentage of HbA1c STANDARD_DEVIATION 0.62 | 8.61 Percentage of HbA1c STANDARD_DEVIATION 0.6 | 8.61 Percentage of HbA1c STANDARD_DEVIATION 0.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 391 Participants | 195 Participants | 586 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 391 Participants | 195 Participants | 586 Participants |
| Sex: Female, Male Female | 113 Participants | 53 Participants | 166 Participants |
| Sex: Female, Male Male | 278 Participants | 142 Participants | 420 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 391 | 0 / 195 |
| other Total, other adverse events | 298 / 391 | 143 / 195 |
| serious Total, serious adverse events | 15 / 391 | 7 / 195 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26
HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Pre-study oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment × Time as variables.
Time frame: Baseline, Week 26
Population: All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention and had at least one post baseline value for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide 1.5 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | -1.53 Percentage of HbA1c | Standard Error 0.043 |
| Dulaglutide 0.75 mg | Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | -1.25 Percentage of HbA1c | Standard Error 0.06 |
p-value: <0.00195% CI: [-0.43, -0.14]Mixed Models Analysis
Secondary
Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG)
SMBG 6-point profiles were measured at morning (premeal-fasting, 2-hour post meal), midday (premeal, 2-hour post meal), and evening (premeal, 2-hour post meal). LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment as variables.
Time frame: Baseline, Week 26
Population: All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention and had at least one post baseline value for this analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Dulaglutide 1.5 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Evening premeal | -50.3 mg/dL | Standard Error 1.6 |
| Dulaglutide 1.5 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Evening 2-hour post meal | -61.1 mg/dL | Standard Error 2.27 |
| Dulaglutide 1.5 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Morning premeal-fasting | -45.6 mg/dL | Standard Error 1.33 |
| Dulaglutide 1.5 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Morning 2-hour post meal | -70.6 mg/dL | Standard Error 2.42 |
| Dulaglutide 1.5 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Midday premeal | -55.3 mg/dL | Standard Error 1.77 |
| Dulaglutide 1.5 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Midday 2-hour post meal | -73.7 mg/dL | Standard Error 2.37 |
| Dulaglutide 0.75 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Morning 2-hour post meal | -60.5 mg/dL | Standard Error 3.39 |
| Dulaglutide 0.75 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Evening premeal | -46.4 mg/dL | Standard Error 2.24 |
| Dulaglutide 0.75 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Midday 2-hour post meal | -61.2 mg/dL | Standard Error 3.32 |
| Dulaglutide 0.75 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Evening 2-hour post meal | -49.8 mg/dL | Standard Error 3.18 |
| Dulaglutide 0.75 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Midday premeal | -47.0 mg/dL | Standard Error 2.47 |
| Dulaglutide 0.75 mg | Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | Morning premeal-fasting | -38.4 mg/dL | Standard Error 1.86 |
Comparison: Morning premeal-fastingp-value: 0.00295% CI: [-11.7, -2.7]ANCOVA
Comparison: Morning 2-hour post mealp-value: 0.01695% CI: [-18.3, -1.9]ANCOVA
Comparison: Midday premealp-value: 0.00795% CI: [-14.2, -2.3]ANCOVA
Comparison: Midday 2-hour post mealp-value: 0.00295% CI: [-20.5, -4.5]ANCOVA
Comparison: Evening premealp-value: 0.15895% CI: [-9.3, 1.5]ANCOVA
Comparison: Evening 2-hour post mealp-value: 0.00495% CI: [-19, -3.7]ANCOVA
Secondary
Change From Baseline in Body Weight
LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment\*Time as variables.
Time frame: Baseline, Week 52
Population: All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention and had at least one post baseline value for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide 1.5 mg | Change From Baseline in Body Weight | -0.5 kilogram (kg) | Standard Error 0.14 |
| Dulaglutide 0.75 mg | Change From Baseline in Body Weight | -0.2 kilogram (kg) | Standard Error 0.19 |
p-value: 0.21395% CI: [-0.8, 0.2]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Serum Glucose (FSG)
FSG is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment\*Time as variables.
Time frame: Baseline, Week 52
Population: All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention and had at least one post baseline value for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide 1.5 mg | Change From Baseline in Fasting Serum Glucose (FSG) | -42.4 milligrams per deciliter (mg/dL) | Standard Error 1.47 |
| Dulaglutide 0.75 mg | Change From Baseline in Fasting Serum Glucose (FSG) | -33.1 milligrams per deciliter (mg/dL) | Standard Error 2.09 |
p-value: <0.00195% CI: [-14.4, -4.3]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c at Week 52
HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables.
Time frame: Baseline, Week 52
Population: All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention and had at least one post baseline value for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide 1.5 mg | Change From Baseline in HbA1c at Week 52 | -1.50 Percentage of HbA1c | Standard Error 0.046 |
| Dulaglutide 0.75 mg | Change From Baseline in HbA1c at Week 52 | -1.19 Percentage of HbA1c | Standard Error 0.065 |
p-value: <0.00195% CI: [-0.47, -0.15]Mixed Models Analysis
Secondary
Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0%
HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The odds ratios, confidence intervals, and p-values were determined by generalized linear mixed model (GLM) with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables.
Time frame: Week 52
Population: All randomly assigned participants, excluding the GCP compliance investigative site, who were exposed to at least 1 dose of study intervention and had at least one post baseline value for this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dulaglutide 1.5 mg | Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% | HbA1c < 7% | 46.33 Percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% | HbA1c ≤ 6.5% | 22.88 Percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% | HbA1c ≤ 6.5% | 21.26 Percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% | HbA1c < 7% | 38.51 Percentage of participants |
Comparison: For HbA1c ≤6.5%p-value: 0.5695% CI: [0.71, 1.87]Generalized Linear Mixed Model (GLM)
Comparison: For HbA1c \< 7%p-value: 0.02895% CI: [1.05, 2.45]Generalized Linear Mixed Model (GLM)