Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of once-weekly dulaglutide compared to placebo in participants with type 2 diabetes who have inadequate glycemic control with sulfonylurea monotherapy.
Interventions
DRUGPlacebo
Administered SQ
DRUGDulaglutide
Administered SQ
DRUGGlimepiride
Administered PO
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus * Stable dose of sulfonylurea that is at least 50% of the maximum approved dose per the local label for at least 3 months prior to the first study visit * Have an HbA1c value of ≥7.5% and ≤9.5%, as determined by the central laboratory draw performed at the first study visit * Accept continued treatment with sulfonylurea therapy, throughout the trial, as required per protocol * Men and nonpregnant women aged ≥18 years * Stable weight (±5%) ≥3 months prior to screening * Body Mass Index (BMI) ≤45 kilograms per square meter (kg/m\^2)
Exclusion criteria
* Have type 1 diabetes mellitus * Have been treated with ANY other antihyperglycemic medications (other than sulfonylurea) at the time of the first study visit or within 3 months prior to the first study visit * Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks; any insulin within 3 months prior to the first study visit is exclusionary * Have been treated with drugs that promote weight loss within 3 months prior to the first study visit * Are receiving chronic (\>14 days) systemic glucocorticoid therapy or have received such therapy within the 4 weeks immediately prior to the first study visit * Have had any of the following Cardiovascular (CV) conditions within 2 months prior to the first study visit: acute myocardial infarction, New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident * Have a known clinically significant gastric emptying abnormality (eg, severe diabetic gastroparesis or gastric outlet obstruction) or have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery * Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or alanine transaminase level \>2.5 times the upper limit of normal * Have a history of chronic pancreatitis or acute idiopathic pancreatitis, or were diagnosed with any type of acute pancreatitis within the 3 month period prior to the first study visit * Have an estimated glomerular filtration rate \[eGFR\] \<30 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2), calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation as determined by the central laboratory at the first study visit * Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia (this exclusion includes those participants with a family history of MEN 2A or 2B, whose family history for the syndrome is Rearranged during Transfection (RET) negative; the only exception for this exclusion will be for participants whose family members with MEN 2A or 2B have a known RET mutation and the potential participant for the study is negative for that RET mutation) * Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma (including sporadic, familial or part of MEN 2A or 2B syndrome) * Have a serum calcitonin ≥20 picogram per milliliter (pg/mL) as determined by the central laboratory at the first study visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 24 Weeks | Baseline, 24 Weeks | Least Squares Means (LS Means) of the HbA1c change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline HbA1c as covariate, via a Mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Serum Glucose (FSG) at 24 Weeks | Baseline, 24 Weeks | LS Means of the FSG from baseline to primary endpoint was adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline FSG as covariate, via Analysis of Covariance Model (ANCOVA) with Last Observation Carried Forward (LOCF). |
| Change From Baseline in Body Weight at 24 Weeks | Baseline, 24 Weeks | LS Means of the body weight change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline body weight as covariate, via a MMRM analysis using REML. |
| Change From Baseline in Body Mass Index (BMI) at 24 Weeks | Baseline, 24 Weeks | LS Means of the BMI change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline BMI as covariate, via a MMRM analysis using REML. |
| Change From Baseline in Calcitonin at 24 Weeks | Baseline, 24 Weeks | — |
| Change From Baseline in Mean of All 7-Point Self Monitored Plasma Glucose (SMPG) at 24 Weeks | Baseline, 24 Weeks | LS Means of the SMPG change from baseline to primary endpoint at week 24 was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline SMPG value as covariate, via a MMRM analysis using REML. |
| Number of Participants With Reported and Adjudicated Cardiovascular Events | Baseline through 24 Weeks, 30-day Follow Up | Information on cardiovascular (CV) risk factors was collected at baseline. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 24 weeks plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module. |
| Number of Participants With Adjudicated Acute Pancreatitis Events | Baseline through 24 Weeks, 30-day Follow Up | The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 24 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks | 24 Weeks | The percentage of participants who achieved the target HbA1c values at endpoint will be analyzed with a repeated logistic regression model (the generalized estimation equation \[GEE\] model). The model includes country, treatment, visit and treatment interaction and baseline HbA1c as a continuous covariate. |
| Rate of HE Adjusted Per 30 Days | Baseline through 24 weeks | The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period\*30 days. |
| Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia | Baseline through 24 Weeks | Additional Intervention: any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. |
| Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia | Baseline through 24 Weeks | An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period. |
| Dulaglutide Anti-Drug Antibodies (ADA) | Baseline up to 4 Weeks Post-Last Dose of Study Drug | Number of participants with treatment emergent (TE) dulaglutide anti-drug antibodies from postbaseline to follow up were summarized. A participant is considered to have TE dulaglutide ADA if the participant has at least one titer that is treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. |
| Change From Baseline in Lipase | Baseline, 24 Weeks | A summary of changes in lipase evaluation from baseline to endpoint. |
| Change From Baseline in Amylase | Baseline, 24 Weeks | A summary of changes in amylase evaluation from baseline to endpoint. |
| Percentage of Participants With Self-Reported Events of Hypoglycemia | Baseline through 24 Weeks | Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<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). Percentage is calculated as the number of participants reporting HE each visit/ the total number of participants reporting HE during the entire study treatment period. |
Countries
Argentina, Austria, Croatia, Mexico, Romania, Slovenia, South Africa, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dulaglutide Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose. | 239 |
| Placebo Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose. | 60 |
| Total | 299 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 0 |
| Overall Study | Entry criteria not met | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Sponsor Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 10 | 3 |
Baseline characteristics
| Characteristic | Dulaglutide | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 57 Participants | 68 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 182 Participants | 231 Participants | 49 Participants |
| Age, Continuous | 57.73 years STANDARD_DEVIATION 10.2 | 57.83 years STANDARD_DEVIATION 9.7 | 58.23 years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 112 Participants | 139 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 127 Participants | 160 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 21 Participants | 26 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 8 Participants | 2 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 | 202 Participants | 249 Participants | 47 Participants |
| Region of Enrollment Argentina | 29 participants | 37 participants | 8 participants |
| Region of Enrollment Austria | 4 participants | 5 participants | 1 participants |
| Region of Enrollment Croatia | 9 participants | 11 participants | 2 participants |
| Region of Enrollment Mexico | 40 participants | 50 participants | 10 participants |
| Region of Enrollment Puerto Rico | 2 participants | 3 participants | 1 participants |
| Region of Enrollment Romania | 78 participants | 96 participants | 18 participants |
| Region of Enrollment Slovenia | 13 participants | 16 participants | 3 participants |
| Region of Enrollment South Africa | 7 participants | 10 participants | 3 participants |
| Region of Enrollment United States | 57 participants | 71 participants | 14 participants |
| Sex: Female, Male Female | 135 Participants | 167 Participants | 32 Participants |
| Sex: Female, Male Male | 104 Participants | 132 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 239 | 3 / 60 |
| serious Total, serious adverse events | 9 / 239 | 0 / 60 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 24 Weeks
Least Squares Means (LS Means) of the HbA1c change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline HbA1c as covariate, via a Mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML).
Time frame: Baseline, 24 Weeks
Population: Participants who were randomized and received at least one dose of study drug with evaluable HbA1c data at both baseline and post-baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 24 Weeks | -1.38 percent change of HbA1c | Standard Error 0.08 |
| Placebo | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 24 Weeks | -0.11 percent change of HbA1c | Standard Error 0.14 |
p-value: <0.00195% CI: [-1.57, -0.97]Mixed Models Analysis
Secondary
Change From Baseline in Amylase
A summary of changes in amylase evaluation from baseline to endpoint.
Time frame: Baseline, 24 Weeks
Population: Participants who received at least one dose of study drug and had evaluable amylase data at both baseline and post-baseline. LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dulaglutide | Change From Baseline in Amylase | 8.0 Units/Liter |
| Placebo | Change From Baseline in Amylase | 2.0 Units/Liter |
Secondary
Change From Baseline in Body Mass Index (BMI) at 24 Weeks
LS Means of the BMI change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline BMI as covariate, via a MMRM analysis using REML.
Time frame: Baseline, 24 Weeks
Population: Participants who received at least one dose of study drug and evaluable BMI data at both baseline and post-baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Change From Baseline in Body Mass Index (BMI) at 24 Weeks | -0.32 kilograms per/square meter kg/m^2 | Standard Error 0.08 |
| Placebo | Change From Baseline in Body Mass Index (BMI) at 24 Weeks | -0.10 kilograms per/square meter kg/m^2 | Standard Error 0.15 |
p-value: 0.16195% CI: [-0.54, 0.09]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight at 24 Weeks
LS Means of the body weight change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline body weight as covariate, via a MMRM analysis using REML.
Time frame: Baseline, 24 Weeks
Population: Participants who received at least one dose of study drug and had evaluable body weight data at both baseline and post-baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Change From Baseline in Body Weight at 24 Weeks | -0.91 kilograms (kg) | Standard Error 0.21 |
| Placebo | Change From Baseline in Body Weight at 24 Weeks | -0.24 kilograms (kg) | Standard Error 0.4 |
p-value: 0.1295% CI: [-1.53, 0.18]Mixed Models Analysis
Secondary
Change From Baseline in Calcitonin at 24 Weeks
Time frame: Baseline, 24 Weeks
Population: Participants who received at least one dose of study drug and evaluable calcitonin data at baseline and post-baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dulaglutide | Change From Baseline in Calcitonin at 24 Weeks | 0.00 picogram per milliliter (pg/ml) |
| Placebo | Change From Baseline in Calcitonin at 24 Weeks | 0.00 picogram per milliliter (pg/ml) |
Secondary
Change From Baseline in Fasting Serum Glucose (FSG) at 24 Weeks
LS Means of the FSG from baseline to primary endpoint was adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline FSG as covariate, via Analysis of Covariance Model (ANCOVA) with Last Observation Carried Forward (LOCF).
Time frame: Baseline, 24 Weeks
Population: Participants who received at least one dose of study drug and had evaluable FSG data at both baseline and post-baseline. LOCF was used to impute missing post-baseline values. If no data after date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Change From Baseline in Fasting Serum Glucose (FSG) at 24 Weeks | -30.60 milligrams per deciliter (mg/dL) | Standard Error 4.46 |
| Placebo | Change From Baseline in Fasting Serum Glucose (FSG) at 24 Weeks | 2.93 milligrams per deciliter (mg/dL) | Standard Error 6.76 |
p-value: <0.00195% CI: [-46.55, -20.53]ANCOVA
Secondary
Change From Baseline in Lipase
A summary of changes in lipase evaluation from baseline to endpoint.
Time frame: Baseline, 24 Weeks
Population: All participants who received at least one dose of study drug and had evaluable lipase data at both baseline and post-baseline. LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dulaglutide | Change From Baseline in Lipase | 8.0 Units/Liter |
| Placebo | Change From Baseline in Lipase | 4.5 Units/Liter |
Secondary
Change From Baseline in Mean of All 7-Point Self Monitored Plasma Glucose (SMPG) at 24 Weeks
LS Means of the SMPG change from baseline to primary endpoint at week 24 was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline SMPG value as covariate, via a MMRM analysis using REML.
Time frame: Baseline, 24 Weeks
Population: Participants who received at least one dose of study drug and had evaluable SMPG data at both baseline and post-baseline.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Change From Baseline in Mean of All 7-Point Self Monitored Plasma Glucose (SMPG) at 24 Weeks | -37.22 mg/dL | Standard Error 3.1 |
| Placebo | Change From Baseline in Mean of All 7-Point Self Monitored Plasma Glucose (SMPG) at 24 Weeks | -8.27 mg/dL | Standard Error 4.77 |
p-value: <0.00195% CI: [-38.49, -19.4]Mixed Models Analysis
Secondary
Dulaglutide Anti-Drug Antibodies (ADA)
Number of participants with treatment emergent (TE) dulaglutide anti-drug antibodies from postbaseline to follow up were summarized. A participant is considered to have TE dulaglutide ADA if the participant has at least one titer that is treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.
Time frame: Baseline up to 4 Weeks Post-Last Dose of Study Drug
Population: ITT population: all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dulaglutide | Dulaglutide Anti-Drug Antibodies (ADA) | 2 participants |
Secondary
Number of Participants With Adjudicated Acute Pancreatitis Events
The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 24 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through 24 Weeks, 30-day Follow Up
Population: ITT population: all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dulaglutide | Number of Participants With Adjudicated Acute Pancreatitis Events | 0 participants |
| Placebo | Number of Participants With Adjudicated Acute Pancreatitis Events | 0 participants |
Secondary
Number of Participants With Reported and Adjudicated Cardiovascular Events
Information on cardiovascular (CV) risk factors was collected at baseline. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 24 weeks plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.
Time frame: Baseline through 24 Weeks, 30-day Follow Up
Population: ITT population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dulaglutide | Number of Participants With Reported and Adjudicated Cardiovascular Events | Any reported CV events | 2 participants |
| Dulaglutide | Number of Participants With Reported and Adjudicated Cardiovascular Events | Any adjudicated nonfatal CV events | 2 participants |
| Dulaglutide | Number of Participants With Reported and Adjudicated Cardiovascular Events | Any confirmed adjudicated CV deaths | 0 participants |
| Placebo | Number of Participants With Reported and Adjudicated Cardiovascular Events | Any reported CV events | 0 participants |
| Placebo | Number of Participants With Reported and Adjudicated Cardiovascular Events | Any adjudicated nonfatal CV events | 0 participants |
| Placebo | Number of Participants With Reported and Adjudicated Cardiovascular Events | Any confirmed adjudicated CV deaths | 0 participants |
Secondary
Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia
Additional Intervention: any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation.
Time frame: Baseline through 24 Weeks
Population: ITT population: all randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dulaglutide | Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia | 2.1 percentage of participants |
| Placebo | Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia | 11.7 percentage of participants |
Secondary
Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks
The percentage of participants who achieved the target HbA1c values at endpoint will be analyzed with a repeated logistic regression model (the generalized estimation equation \[GEE\] model). The model includes country, treatment, visit and treatment interaction and baseline HbA1c as a continuous covariate.
Time frame: 24 Weeks
Population: Participants who were randomized and received at least one dose of study drug with evaluable HbA1c data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dulaglutide | Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks | Percent Achieved <7.0 HbA1c Level | 55.3 percentage of participants |
| Dulaglutide | Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks | Percent Achieved ≤6.5 HbA1c Level | 40.0 percentage of participants |
| Placebo | Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks | Percent Achieved <7.0 HbA1c Level | 18.9 percentage of participants |
| Placebo | Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks | Percent Achieved ≤6.5 HbA1c Level | 9.4 percentage of participants |
Comparison: \<7.0% HbA1cp-value: <0.00195% CI: [3.82, 33.84]Regression, Logistic
Comparison: ≤6.5% HbA1cp-value: <0.00195% CI: [3.71, 35.34]Regression, Logistic
Secondary
Percentage of Participants With Self-Reported Events of Hypoglycemia
Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =\<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =\<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). Percentage is calculated as the number of participants reporting HE each visit/ the total number of participants reporting HE during the entire study treatment period.
Time frame: Baseline through 24 Weeks
Population: ITT Population: all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dulaglutide | Percentage of Participants With Self-Reported Events of Hypoglycemia | Asymptomatic | 13.4 percentage of participants |
| Dulaglutide | Percentage of Participants With Self-Reported Events of Hypoglycemia | Severe | 0 percentage of participants |
| Dulaglutide | Percentage of Participants With Self-Reported Events of Hypoglycemia | Probable | 2.5 percentage of participants |
| Dulaglutide | Percentage of Participants With Self-Reported Events of Hypoglycemia | Nocturnal | 6.7 percentage of participants |
| Dulaglutide | Percentage of Participants With Self-Reported Events of Hypoglycemia | Symptomatic | 11.3 percentage of participants |
| Placebo | Percentage of Participants With Self-Reported Events of Hypoglycemia | Nocturnal | 1.7 percentage of participants |
| Placebo | Percentage of Participants With Self-Reported Events of Hypoglycemia | Symptomatic | 1.7 percentage of participants |
| Placebo | Percentage of Participants With Self-Reported Events of Hypoglycemia | Asymptomatic | 1.7 percentage of participants |
| Placebo | Percentage of Participants With Self-Reported Events of Hypoglycemia | Probable | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Self-Reported Events of Hypoglycemia | Severe | 0 percentage of participants |
Secondary
Rate of HE Adjusted Per 30 Days
The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period\*30 days.
Time frame: Baseline through 24 weeks
Population: ITT population: all randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dulaglutide | Rate of HE Adjusted Per 30 Days | Total HE | 0.19 number of events/participants/30 days | Standard Deviation 0.59 |
| Dulaglutide | Rate of HE Adjusted Per 30 Days | Documented symptomatic HE | 0.07 number of events/participants/30 days | Standard Deviation 0.33 |
| Dulaglutide | Rate of HE Adjusted Per 30 Days | Asymptomatic HE | 0.11 number of events/participants/30 days | Standard Deviation 0.45 |
| Dulaglutide | Rate of HE Adjusted Per 30 Days | Severe HE | 0 number of events/participants/30 days | Standard Deviation 0 |
| Dulaglutide | Rate of HE Adjusted Per 30 Days | Nocturnal HE | 0.02 number of events/participants/30 days | Standard Deviation 0.16 |
| Dulaglutide | Rate of HE Adjusted Per 30 Days | Probable symptomatic HE | 0.01 number of events/participants/30 days | Standard Deviation 0.04 |
| Placebo | Rate of HE Adjusted Per 30 Days | Nocturnal HE | 0.00 number of events/participants/30 days | Standard Deviation 0.02 |
| Placebo | Rate of HE Adjusted Per 30 Days | Total HE | 0.01 number of events/participants/30 days | Standard Deviation 0.03 |
| Placebo | Rate of HE Adjusted Per 30 Days | Severe HE | 0 number of events/participants/30 days | Standard Deviation 0 |
| Placebo | Rate of HE Adjusted Per 30 Days | Documented symptomatic HE | 0.00 number of events/participants/30 days | Standard Deviation 0.02 |
| Placebo | Rate of HE Adjusted Per 30 Days | Probable symptomatic HE | 0 number of events/participants/30 days | Standard Deviation 0 |
| Placebo | Rate of HE Adjusted Per 30 Days | Asymptomatic HE | 0.00 number of events/participants/30 days | Standard Deviation 0.02 |
Secondary
Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia
An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period.
Time frame: Baseline through 24 Weeks
Population: ITT population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia | 22.59 weeks | Standard Error 0.36 |
| Placebo | Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia | 22.47 weeks | Standard Error 0.66 |