Chronic Kidney Disease, Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to determine the glycemic efficacy and safety of dulaglutide compared to insulin glargine in the treatment of participants with type 2 diabetes and moderate or severe chronic kidney disease.
Interventions
DRUGDulaglutide
Administered SC
DRUGInsulin glargine
Administered SC
DRUGInsulin lispro
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Dulaglutide dose was blinded to participant, care provider, investigator and outcomes assessor.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and non-pregnant women aged ≥18 years * Hemoglobin A1c (HbA1c) ≥7.5% and ≤10.5% * Type 2 diabetes on insulin or insulin + oral antihyperglycemic medication * Participants with presumed diabetic kidney disease with or without hypertensive nephrosclerosis diagnosed with moderate or severe CKD with estimated glomerular filtration rate (eGFR) of ≥15 to \<60 milliliters per minute (mL/min)/1.73 meter squared (m\^2) * Able and willing to perform multiple daily injections * Body mass index (BMI) between 23 and 45 kilogram/square meter (kg/m\^2)
Exclusion criteria
* Stage 5 CKD as defined by eGFR \<15 mL/min/1.73 m\^2 OR having required dialysis * Rapidly progressing renal dysfunction likely to require renal replacement * History of a transplanted organ * Type 1 diabetes mellitus * At screening a systolic blood pressure of ≥150 mmHg or a diastolic blood pressure of ≥90 mmHg with or without antihypertensive medication * An episode of ketoacidosis or hyperosmolar state/coma in the past 6 months or a history of severe hypoglycemia in the past 3 months prior to the Screening Visit * Cardiovascular conditions within 12 weeks prior to randomization: acute myocardial infarction, New York Heart Association (NYHA) class III or class IV heart failure, or cerebrovascular accident (stroke) * Acute or chronic hepatitis * Signs and symptoms of chronic or acute pancreatitis, or were in the past diagnosed with pancreatitis * Serum calcitonin ≥35 picograms per milliliter (pg/mL) at Screening Visit * Self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma * Known history of untreated proliferative retinopathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) | 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 in HbA1c were calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, macroalbuminuria (MA) region, Baseline CKD Severity, week, treatment\*week, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Whose HbA1c Was <8.0% | 26 Weeks | Percentage of Participants whose HbA1c was \<8.0% based on last observation carried forward (LOCF). |
| Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG) | Baseline, 26 Weeks | The daily mean of 8-point SMPG profile at Week 26 is presented. Participants were required to perform two 8-point SMPG profiles over a 1-week period at 5 separate times throughout the study. LS means were calculated using the MMRM model including the corresponding baseline value as a continuous covariate, as well as baseline HbA1c, MA-region, treatment, week, treatment\*week, baseline CKD severity, and log baseline eGFR (within CKD severity).The two 8-point SMPG profiles were collected on two non-consecutive days (pre-meal and 2-hour postprandial SMPG x \[morning, midday, and evening meals in one day\] + bedtime + 5 hours after bedtime). |
| Change From Baseline in Fasting Glucose (FG) | Baseline, 26 Weeks | LS means were calculated using MMRM with the change in FG as the dependent variable and treatment, MA -region, Baseline CKD Severity, week, treatment\*week, baseline FG, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured |
| Change From Baseline in Mean Daily Insulin Lispro Dose | Baseline, 26 Weeks | The mean daily insulin was based on a 4-week interval prior to week 26 assessments. LS means were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in mean daily insulin as the dependent variable and treatment, MA-region, Baseline HbA1c, baseline mean daily insulin, baseline CKD Severity, week, treatment\*week, log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured. |
| Percentage of Participants With Estimated Average Glucose <154 mg/dL | 26 Weeks | Percentage of Participants With Estimated Average Glucose \<154 milligram/deciliter (mg/dL) was based on last observation carried forward (LOCF). |
| Change From Baseline in Serum Creatinine (sCr) | Baseline, 26 Weeks | Change from baseline in serum creatinine (sCr) levels after treatment. |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | Baseline, 26 Weeks | The change in estimated glomerular filtration rate (eGFR) by using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. |
| Change From Baseline in Estimated Creatinine Clearance (eCrCl) | Baseline, 26 Weeks | Estimated creatinine clearance (eCrCl) was calculated by Cockcroft-Gault \[Cockcroft and Gault 1976\] equation using baseline estimated lean body weight. |
| Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) | Baseline, 26 Weeks | The change from baseline in Urinary Albumin to Creatinine Ratio (UACR). |
| Change From Baseline in Body Weight | Baseline, 26 Weeks | LS means were calculated from a REML based MMRM model: Change from Baseline = treatment, week, treatment\*Week, MA-region, Baseline HbA1c (%), Baseline Body Weight (kg), Baseline CKD Severity, Log Baseline eGFR (within CKD severity), where participant enters the model as a random effect. Covariance structure = Unstructured. • |
| Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Baseline through 26 Weeks | Hypoglycemic events (HE) were classified as severe (defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other 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 (≤70 mg/dL), nocturnal (defined as any hypoglycemic event that occurs between bedtime and waking). The number of self-reported hypoglycemic events was summarized cumulatively at 26 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section. |
| Rate of Hypoglycemic Events | Baseline through 26 Weeks | Hypoglycemic events (HE) were classified as total HE rate, documented symptomatic hypoglycemia, severe hypoglycemia, and nocturnal. The 1-year adjusted rate of HEs was summarized cumulatively at 26 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section. |
| Percentage of Participants Whose HbA1c Was <7.0% | 26 Weeks | Percentage of participants whose HbA1c was \<7.0% based on last observation carried forward (LOCF). |
| Percentage of Participants Whose HbA1c is <7.0% | 52 Weeks | Percentage of participants whose HbA1c was \<7.0% based on last observation carried forward (LOCF). |
| Percentage of Participants Whose HbA1c is <8.0% | 52 Weeks | Percentage of participants whose HbA1c was \<8.0% based on last observation carried forward (LOCF). |
| Change From Baseline in 8-Point SMPG | Baseline, 52 Weeks | The daily mean of 8-point SMPG profile at Week 52 is presented. Participants were required to perform two 8-point SMPG profiles over a 1-week period at 5 separate times throughout the study. LS means were calculated using the MMRM model including the corresponding baseline value as a continuous covariate, as well as baseline HbA1c, MA-region, treatment, week, treatment\*week, baseline CKD severity, and log baseline eGFR (within CKD severity).The two 8-point SMPG profiles were collected on two non-consecutive days (pre-meal and 2-hour postprandial SMPG x \[morning, midday, and evening meals in one day\] + bedtime + 5 hours after bedtime). |
| Change From Baseline in FG | Baseline, 52 Weeks | LS means were calculated using MMRM with the change in FG as the dependent variable and treatment, MA -region, Baseline CKD Severity, week, treatment\*week, baseline FG, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured |
| Change in Mean Daily Insulin Lispro Dose | Baseline, 52 Weeks | The mean daily insulin was based on a 4-week interval prior to week 52 assessments. LS means were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in mean daily insulin as the dependent variable and treatment, MA-region, Baseline HbA1c, baseline mean daily insulin, baseline CKD Severity, week, treatment\*week, log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured. |
| Change From Baseline in sCr | Baseline, 52 Weeks | Change from baseline in sCr levels after treatment. |
| Change From Baseline in eGFR | Baseline, 52 Weeks | The change in eGFR by using CKD-EPI equation. |
| Change From Baseline in eCrCl | Baseline, 52 Weeks | eCrCl was calculated by Cockcroft-Gault \[Cockcroft and Gault 1976\] equation using baseline estimated lean body weight. |
| Change From Baseline in UACR | Baseline, 52 Weeks | The change from baseline in UACR |
| Rate of Hypoglycemic Events (HE) | Baseline through 52 Weeks | HE were classified as total HE rate, documented symptomatic hypoglycemia, severe hypoglycemia, and nocturnal. The 1-year adjusted rate of HEs was summarized cumulatively at 52 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section. |
| Participants With Events of Allergic/Hypersensitivity Reactions | Baseline through 52 Weeks | Participants with Events of Allergic/Hypersensitivity Reactions: Angioedema Standardized MedDRA Query (SMQ), Anaphylactic Reaction SMQ, or Severe Cutaneous Adverse Reactions SMQ |
| Change From Baseline in HbA1c | 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 in HbA1c were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, MA region, Baseline CKD Severity, week, treatment\*week, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured. |
Countries
Brazil, Hungary, Mexico, Poland, Romania, South Africa, Spain, Ukraine, United States
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 |
|---|---|
| Insulin Glargine Insulin glargine was administered SC at bedtime per a modified forced-titration treat-to-target algorithm. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day. | 194 |
| Dulaglutide 0.75 mg Dulaglutide 0.75 mg administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day. | 190 |
| Dulaglutide 1.5 mg Dulaglutide 1.5 mg administered once weekly as a SC injection. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day. | 192 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 8 |
| Overall Study | Death | 6 | 7 | 2 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
| Overall Study | Physician Decision | 5 | 2 | 7 |
| Overall Study | Withdrawal by Subject | 14 | 17 | 18 |
Baseline characteristics
| Characteristic | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 8.41 | 64.7 years STANDARD_DEVIATION 8.61 | 64.7 years STANDARD_DEVIATION 8.83 | 64.6 years STANDARD_DEVIATION 8.6 |
| Body Mass Index (BMI) | 32.39 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 5.324 | 33.00 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 5.546 | 32.11 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 4.841 | 32.50 kilogram/square meter (kg/m^2) STANDARD_DEVIATION 5.248 |
| Body Weight | 88.20 kilogram (kg) STANDARD_DEVIATION 18.488 | 90.88 kilogram (kg) STANDARD_DEVIATION 18.301 | 88.14 kilogram (kg) STANDARD_DEVIATION 16.015 | 89.06 kilogram (kg) STANDARD_DEVIATION 17.653 |
| Duration of Chronic Kidney Disease (CKD) Stage 3 or Higher | 3.47 years STANDARD_DEVIATION 3.998 | 4.03 years STANDARD_DEVIATION 4.854 | 4.18 years STANDARD_DEVIATION 5.632 | 3.89 years STANDARD_DEVIATION 4.872 |
| Duration of Diabetes | 18.71 years STANDARD_DEVIATION 8.742 | 17.95 years STANDARD_DEVIATION 8.788 | 17.57 years STANDARD_DEVIATION 8.722 | 18.08 years STANDARD_DEVIATION 8.748 |
| Estimated Glomerular Filtration Rate (eGFR) | 38.5 milliliter/minute/1.73 square meter STANDARD_DEVIATION 12.99 | 38.3 milliliter/minute/1.73 square meter STANDARD_DEVIATION 12.31 | 38.1 milliliter/minute/1.73 square meter STANDARD_DEVIATION 13.24 | 38.3 milliliter/minute/1.73 square meter STANDARD_DEVIATION 12.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 79 Participants | 75 Participants | 78 Participants | 232 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 115 Participants | 115 Participants | 114 Participants | 344 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1C (HbA1c) at Baseline | 8.56 Percentage of HbA1c STANDARD_DEVIATION 0.966 | 8.57 Percentage of HbA1c STANDARD_DEVIATION 1.088 | 8.59 Percentage of HbA1c STANDARD_DEVIATION 0.86 | 8.57 Percentage of HbA1c STANDARD_DEVIATION 0.973 |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 17 Participants | 12 Participants | 47 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 7 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 36 Participants | 26 Participants | 88 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 7 Participants | 10 Participants | 23 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) White | 137 Participants | 122 Participants | 134 Participants | 393 Participants |
| Region of Enrollment Brazil | 44 Participants | 47 Participants | 50 Participants | 141 Participants |
| Region of Enrollment Hungary | 22 Participants | 19 Participants | 14 Participants | 55 Participants |
| Region of Enrollment Mexico | 19 Participants | 19 Participants | 15 Participants | 53 Participants |
| Region of Enrollment Poland | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Romania | 14 Participants | 9 Participants | 14 Participants | 37 Participants |
| Region of Enrollment South Africa | 14 Participants | 20 Participants | 17 Participants | 51 Participants |
| Region of Enrollment Spain | 2 Participants | 4 Participants | 6 Participants | 12 Participants |
| Region of Enrollment Ukraine | 17 Participants | 11 Participants | 12 Participants | 40 Participants |
| Region of Enrollment United States | 61 Participants | 59 Participants | 62 Participants | 182 Participants |
| Sex: Female, Male Female | 101 Participants | 86 Participants | 88 Participants | 275 Participants |
| Sex: Female, Male Male | 93 Participants | 104 Participants | 104 Participants | 301 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 | 130 / 194 | 134 / 190 | 144 / 192 |
| serious Total, serious adverse events | 56 / 194 | 48 / 190 | 41 / 192 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c)
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 in HbA1c were calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, macroalbuminuria (MA) region, Baseline CKD Severity, week, treatment\*week, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.13 percentage of HbA1c | Standard Error 0.12 |
| Dulaglutide 0.75 mg | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.12 percentage of HbA1c | Standard Error 0.12 |
| Dulaglutide 1.5 mg | Change From Baseline in Hemoglobin A1c (HbA1c) | -1.19 percentage of HbA1c | Standard Error 0.13 |
Comparison: Week 26p-value: <0.00195% CI: [-0.26, 0.15]Mixed Models Analysis
Comparison: Week 26p-value: <0.00195% CI: [-0.18, 0.22]Mixed Models Analysis
Secondary
Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG)
The daily mean of 8-point SMPG profile at Week 26 is presented. Participants were required to perform two 8-point SMPG profiles over a 1-week period at 5 separate times throughout the study. LS means were calculated using the MMRM model including the corresponding baseline value as a continuous covariate, as well as baseline HbA1c, MA-region, treatment, week, treatment\*week, baseline CKD severity, and log baseline eGFR (within CKD severity).The two 8-point SMPG profiles were collected on two non-consecutive days (pre-meal and 2-hour postprandial SMPG x \[morning, midday, and evening meals in one day\] + bedtime + 5 hours after bedtime).
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c and SMPG data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG) | -37.6 milligrams/deciliter (mg/dL) | Standard Error 3.41 |
| Dulaglutide 0.75 mg | Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG) | -31.7 milligrams/deciliter (mg/dL) | Standard Error 3.53 |
| Dulaglutide 1.5 mg | Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG) | -33.7 milligrams/deciliter (mg/dL) | Standard Error 3.77 |
Secondary
Change From Baseline in 8-Point SMPG
The daily mean of 8-point SMPG profile at Week 52 is presented. Participants were required to perform two 8-point SMPG profiles over a 1-week period at 5 separate times throughout the study. LS means were calculated using the MMRM model including the corresponding baseline value as a continuous covariate, as well as baseline HbA1c, MA-region, treatment, week, treatment\*week, baseline CKD severity, and log baseline eGFR (within CKD severity).The two 8-point SMPG profiles were collected on two non-consecutive days (pre-meal and 2-hour postprandial SMPG x \[morning, midday, and evening meals in one day\] + bedtime + 5 hours after bedtime).
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c and SMPG data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in 8-Point SMPG | -40.5 mg/dL | Standard Error 3.59 |
| Dulaglutide 0.75 mg | Change From Baseline in 8-Point SMPG | -30.0 mg/dL | Standard Error 3.75 |
| Dulaglutide 1.5 mg | Change From Baseline in 8-Point SMPG | -27.2 mg/dL | Standard Error 3.93 |
Secondary
Change From Baseline in Body Weight
LS means were calculated from a REML based MMRM model: Change from Baseline = treatment, week, treatment\*Week, MA-region, Baseline HbA1c (%), Baseline Body Weight (kg), Baseline CKD Severity, Log Baseline eGFR (within CKD severity), where participant enters the model as a random effect. Covariance structure = Unstructured. •
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline body weight data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Body Weight | 1.11 kilogram (kg) | Standard Error 0.346 |
| Dulaglutide 0.75 mg | Change From Baseline in Body Weight | -2.02 kilogram (kg) | Standard Error 0.357 |
| Dulaglutide 1.5 mg | Change From Baseline in Body Weight | -2.81 kilogram (kg) | Standard Error 0.374 |
Secondary
Change From Baseline in Body Weight
LS means were calculated from a REML based MMRM model: Change from Baseline = treatment , week, treatment\*Week, MA-region, Baseline HbA1c (%), Baseline Body Weight (kg), Baseline CKD Severity, Log Baseline eGFR (within CKD severity), where participant enters the model as a random effect. Covariance structure = Unstructured.
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline body weight data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Body Weight | 1.57 kg | Standard Error 0.429 |
| Dulaglutide 0.75 mg | Change From Baseline in Body Weight | -1.71 kg | Standard Error 0.448 |
| Dulaglutide 1.5 mg | Change From Baseline in Body Weight | -2.66 kg | Standard Error 0.467 |
Secondary
Change From Baseline in eCrCl
eCrCl was calculated by Cockcroft-Gault \[Cockcroft and Gault 1976\] equation using baseline estimated lean body weight.
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline eCrCl data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in eCrCl | -2.5 mL/min |
| Dulaglutide 0.75 mg | Change From Baseline in eCrCl | -1.3 mL/min |
| Dulaglutide 1.5 mg | Change From Baseline in eCrCl | -1.5 mL/min |
Secondary
Change From Baseline in eGFR
The change in eGFR by using CKD-EPI equation.
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline eGFR data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in eGFR | -3.3 mL/min/1.73m2 |
| Dulaglutide 0.75 mg | Change From Baseline in eGFR | -1.5 mL/min/1.73m2 |
| Dulaglutide 1.5 mg | Change From Baseline in eGFR | -2.0 mL/min/1.73m2 |
Secondary
Change From Baseline in Estimated Creatinine Clearance (eCrCl)
Estimated creatinine clearance (eCrCl) was calculated by Cockcroft-Gault \[Cockcroft and Gault 1976\] equation using baseline estimated lean body weight.
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline eCrCl data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in Estimated Creatinine Clearance (eCrCl) | -2.0 milliliter/minute (ml/min) |
| Dulaglutide 0.75 mg | Change From Baseline in Estimated Creatinine Clearance (eCrCl) | -1.0 milliliter/minute (ml/min) |
| Dulaglutide 1.5 mg | Change From Baseline in Estimated Creatinine Clearance (eCrCl) | -0.5 milliliter/minute (ml/min) |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
The change in estimated glomerular filtration rate (eGFR) by using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation.
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline eGFR data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | -2.5 milliliter/minute/1.73m2 (mL/min/1.73m2) |
| Dulaglutide 0.75 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | -1.0 milliliter/minute/1.73m2 (mL/min/1.73m2) |
| Dulaglutide 1.5 mg | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | -1.0 milliliter/minute/1.73m2 (mL/min/1.73m2) |
Secondary
Change From Baseline in Fasting Glucose (FG)
LS means were calculated using MMRM with the change in FG as the dependent variable and treatment, MA -region, Baseline CKD Severity, week, treatment\*week, baseline FG, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline HbA1c and FG data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Fasting Glucose (FG) | -19.1 milligram/deciliter (mg/dL) | Standard Deviation 6 |
| Dulaglutide 0.75 mg | Change From Baseline in Fasting Glucose (FG) | 17.7 milligram/deciliter (mg/dL) | Standard Deviation 6.14 |
| Dulaglutide 1.5 mg | Change From Baseline in Fasting Glucose (FG) | 23.1 milligram/deciliter (mg/dL) | Standard Deviation 6.5 |
Secondary
Change From Baseline in FG
LS means were calculated using MMRM with the change in FG as the dependent variable and treatment, MA -region, Baseline CKD Severity, week, treatment\*week, baseline FG, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c and FG data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in FG | -6.4 mg/dL | Standard Error 6.38 |
| Dulaglutide 0.75 mg | Change From Baseline in FG | 20.8 mg/dL | Standard Error 6.58 |
| Dulaglutide 1.5 mg | Change From Baseline in FG | 28.3 mg/dL | Standard Error 6.87 |
Secondary
Change From Baseline in HbA1c
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS means in HbA1c were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in HbA1c as the dependent variable and treatment, MA region, Baseline CKD Severity, week, treatment\*week, baseline HbA1c (%), log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in HbA1c | -1.00 percentage of HbA1c | Standard Error 0.12 |
| Dulaglutide 0.75 mg | Change From Baseline in HbA1c | -1.10 percentage of HbA1c | Standard Error 0.12 |
| Dulaglutide 1.5 mg | Change From Baseline in HbA1c | -1.10 percentage of HbA1c | Standard Error 0.13 |
Secondary
Change From Baseline in Mean Daily Insulin Lispro Dose
The mean daily insulin was based on a 4-week interval prior to week 26 assessments. LS means were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in mean daily insulin as the dependent variable and treatment, MA-region, Baseline HbA1c, baseline mean daily insulin, baseline CKD Severity, week, treatment\*week, log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline HbA1c and insulin lispro dose data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change From Baseline in Mean Daily Insulin Lispro Dose | 16.64 Units/day (U/day) | Standard Error 2.76 |
| Dulaglutide 0.75 mg | Change From Baseline in Mean Daily Insulin Lispro Dose | 26.16 Units/day (U/day) | Standard Error 2.8 |
| Dulaglutide 1.5 mg | Change From Baseline in Mean Daily Insulin Lispro Dose | 18.12 Units/day (U/day) | Standard Error 3 |
Secondary
Change From Baseline in sCr
Change from baseline in sCr levels after treatment.
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline sCr data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in sCr | 0.12 mg/dL |
| Dulaglutide 0.75 mg | Change From Baseline in sCr | 0.04 mg/dL |
| Dulaglutide 1.5 mg | Change From Baseline in sCr | 0.07 mg/dL |
Secondary
Change From Baseline in Serum Creatinine (sCr)
Change from baseline in serum creatinine (sCr) levels after treatment.
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline sCr data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in Serum Creatinine (sCr) | 0.10 mg/dL |
| Dulaglutide 0.75 mg | Change From Baseline in Serum Creatinine (sCr) | 0.02 mg/dL |
| Dulaglutide 1.5 mg | Change From Baseline in Serum Creatinine (sCr) | 0.04 mg/dL |
Secondary
Change From Baseline in UACR
The change from baseline in UACR
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline UACR data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in UACR | 3.5 g/kg |
| Dulaglutide 0.75 mg | Change From Baseline in UACR | -3.0 g/kg |
| Dulaglutide 1.5 mg | Change From Baseline in UACR | -11.5 g/kg |
Secondary
Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR)
The change from baseline in Urinary Albumin to Creatinine Ratio (UACR).
Time frame: Baseline, 26 Weeks
Population: All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline UACR data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Glargine | Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) | -1.3 gram/kilogram (g/kg) |
| Dulaglutide 0.75 mg | Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) | -11.1 gram/kilogram (g/kg) |
| Dulaglutide 1.5 mg | Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) | -10.2 gram/kilogram (g/kg) |
Secondary
Change in Mean Daily Insulin Lispro Dose
The mean daily insulin was based on a 4-week interval prior to week 52 assessments. LS means were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in mean daily insulin as the dependent variable and treatment, MA-region, Baseline HbA1c, baseline mean daily insulin, baseline CKD Severity, week, treatment\*week, log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.
Time frame: Baseline, 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline HbA1c and insulin lispro dose data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine | Change in Mean Daily Insulin Lispro Dose | 16.84 U/day | Standard Error 2.87 |
| Dulaglutide 0.75 mg | Change in Mean Daily Insulin Lispro Dose | 27.46 U/day | Standard Error 2.93 |
| Dulaglutide 1.5 mg | Change in Mean Daily Insulin Lispro Dose | 20.05 U/day | Standard Error 3.13 |
Secondary
Participants With Events of Allergic/Hypersensitivity Reactions
Participants with Events of Allergic/Hypersensitivity Reactions: Angioedema Standardized MedDRA Query (SMQ), Anaphylactic Reaction SMQ, or Severe Cutaneous Adverse Reactions SMQ
Time frame: Baseline through 52 Weeks
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Angioedema SMQ | 1 participants with events |
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Angioedema | 0 participants with events |
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Eyelid edema | 0 participants with events |
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Face edema | 0 participants with events |
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Urticaria | 1 participants with events |
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Anaphylactic Reaction SMQ | 1 participants with events |
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Circulatory collapse | 1 participants with events |
| Insulin Glargine | Participants With Events of Allergic/Hypersensitivity Reactions | Severe Cutaneous Adverse Reactions SMQ | 0 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Eyelid edema | 1 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Circulatory collapse | 0 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Face edema | 1 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Urticaria | 0 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Anaphylactic Reaction SMQ | 0 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Angioedema SMQ | 2 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Angioedema | 0 participants with events |
| Dulaglutide 0.75 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Severe Cutaneous Adverse Reactions SMQ | 0 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Eyelid edema | 0 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Angioedema | 1 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Angioedema SMQ | 2 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Face edema | 1 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Circulatory collapse | 0 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Anaphylactic Reaction SMQ | 0 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Urticaria | 0 participants with events |
| Dulaglutide 1.5 mg | Participants With Events of Allergic/Hypersensitivity Reactions | Severe Cutaneous Adverse Reactions SMQ | 0 participants with events |
Secondary
Percentage of Participants Whose HbA1c is <7.0%
Percentage of participants whose HbA1c was \<7.0% based on last observation carried forward (LOCF).
Time frame: 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants Whose HbA1c is <7.0% | 29.1 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants Whose HbA1c is <7.0% | 33.5 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants Whose HbA1c is <7.0% | 32.9 percentage of participants |
Secondary
Percentage of Participants Whose HbA1c is <8.0%
Percentage of participants whose HbA1c was \<8.0% based on last observation carried forward (LOCF).
Time frame: 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants Whose HbA1c is <8.0% | 70.3 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants Whose HbA1c is <8.0% | 69.5 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants Whose HbA1c is <8.0% | 69.1 percentage of participants |
Secondary
Percentage of Participants Whose HbA1c Was <7.0%
Percentage of participants whose HbA1c was \<7.0% based on last observation carried forward (LOCF).
Time frame: 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants Whose HbA1c Was <7.0% | 34.6 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants Whose HbA1c Was <7.0% | 31.7 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants Whose HbA1c Was <7.0% | 37.5 percentage of participants |
Secondary
Percentage of Participants Whose HbA1c Was <8.0%
Percentage of Participants whose HbA1c was \<8.0% based on last observation carried forward (LOCF).
Time frame: 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable post-baseline HbA1c data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants Whose HbA1c Was <8.0% | 75.3 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants Whose HbA1c Was <8.0% | 72.6 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants Whose HbA1c Was <8.0% | 78.3 percentage of participants |
Secondary
Percentage of Participants With Estimated Average Glucose <154 mg/dL
Percentage of Participants With Estimated Average Glucose \<154 milligram/deciliter (mg/dL) was based on last observation carried forward (LOCF).
Time frame: 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable HbA1c and average self-monitored plasma glucose post-baseline data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants With Estimated Average Glucose <154 mg/dL | 64.9 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Estimated Average Glucose <154 mg/dL | 52.5 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Estimated Average Glucose <154 mg/dL | 56.4 percentage of participants |
Secondary
Percentage of Participants With Estimated Average Glucose <154 mg/dL
Percentage of Participants With Estimated Average Glucose \<154 milligram/deciliter (mg/dL) was based on last observation carried forward (LOCF).
Time frame: 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable HbA1c and average self-monitored plasma glucose post-baseline data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine | Percentage of Participants With Estimated Average Glucose <154 mg/dL | 73.7 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Estimated Average Glucose <154 mg/dL | 57.4 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Estimated Average Glucose <154 mg/dL | 50.9 percentage of participants |
Secondary
Percentage of Participants With Self-Reported Hypoglycemic Events (HE)
Hypoglycemic events (HE) were classified as severe (defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other 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 (≤70 mg/dL), nocturnal (defined as any hypoglycemic event that occurs between bedtime and waking). The number of self-reported hypoglycemic events was summarized cumulatively at 52 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through 52 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable post-baseline HE data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Total Hypo | 74.7 percentage of participants |
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Documented Symptomatic Hypo | 63.4 percentage of participants |
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Severe Hypo | 6.7 percentage of participants |
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Nocturnal Hypo | 47.9 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Nocturnal Hypo | 23.8 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Total Hypo | 59.8 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Severe Hypo | 2.6 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Documented Symptomatic Hypo | 48.1 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Severe Hypo | 0 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Documented Symptomatic Hypo | 40.5 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Nocturnal Hypo | 20.5 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Total Hypo | 50.0 percentage of participants |
Secondary
Percentage of Participants With Self-Reported Hypoglycemic Events (HE)
Hypoglycemic events (HE) were classified as severe (defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other 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 (≤70 mg/dL), nocturnal (defined as any hypoglycemic event that occurs between bedtime and waking). The number of self-reported hypoglycemic events was summarized cumulatively at 26 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through 26 Weeks
Population: All randomized participants who received at least one dose of study drug and had evaluable post-baseline HE data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Total Hypo | 71.6 percentage of participants |
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Documented Symptomatic Hypo | 60.3 percentage of participants |
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Severe Hypo | 4.1 percentage of participants |
| Insulin Glargine | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Nocturnal Hypo | 38.1 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Nocturnal Hypo | 15.9 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Total Hypo | 50.8 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Severe Hypo | 1.1 percentage of participants |
| Dulaglutide 0.75 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Documented Symptomatic Hypo | 40.7 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Nocturnal Hypo | 13.2 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Documented Symptomatic Hypo | 31.6 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Severe Hypo | 0 percentage of participants |
| Dulaglutide 1.5 mg | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) | Total Hypo | 43.2 percentage of participants |
Secondary
Rate of Hypoglycemic Events
Hypoglycemic events (HE) were classified as total HE rate, documented symptomatic hypoglycemia, severe hypoglycemia, and nocturnal. The 1-year adjusted rate of HEs was summarized cumulatively at 26 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through 26 Weeks
Population: All randomized participants who had received at least one dose of study drug and had evaluable post-baseline HE rate data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Rate of Hypoglycemic Events | Total HE Rate | 17.07 Events/Participant/Year | Standard Deviation 27.7 |
| Insulin Glargine | Rate of Hypoglycemic Events | Documented Symptomatic HE Rate | 11.34 Events/Participant/Year | Standard Deviation 22.04 |
| Insulin Glargine | Rate of Hypoglycemic Events | Severe HE Rate | 0.10 Events/Participant/Year | Standard Deviation 0.56 |
| Insulin Glargine | Rate of Hypoglycemic Events | Nocturnal HE Rate | 3.06 Events/Participant/Year | Standard Deviation 7.26 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events | Nocturnal HE Rate | 0.73 Events/Participant/Year | Standard Deviation 2.25 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events | Total HE Rate | 7.76 Events/Participant/Year | Standard Deviation 20.39 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events | Severe HE Rate | 0.03 Events/Participant/Year | Standard Deviation 0.31 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events | Documented Symptomatic HE Rate | 4.86 Events/Participant/Year | Standard Deviation 13.37 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events | Nocturnal HE Rate | 0.63 Events/Participant/Year | Standard Deviation 2.26 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events | Documented Symptomatic HE Rate | 4.19 Events/Participant/Year | Standard Deviation 11.58 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events | Severe HE Rate | 0.00 Events/Participant/Year | Standard Deviation 0 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events | Total HE Rate | 5.45 Events/Participant/Year | Standard Deviation 12.54 |
Secondary
Rate of Hypoglycemic Events (HE)
HE were classified as total HE rate, documented symptomatic hypoglycemia, severe hypoglycemia, and nocturnal. The 1-year adjusted rate of HEs was summarized cumulatively at 52 weeks. A summary of other nonserious AEs, and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through 52 Weeks
Population: All randomized participants who had received at least one dose of study drug and had evaluable post-baseline HE rate data. Only measurements prior to rescue or study drug discontinuation were used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Glargine | Rate of Hypoglycemic Events (HE) | Total HE Rate | 14.36 Events/Participant/Year | Standard Deviation 22.2 |
| Insulin Glargine | Rate of Hypoglycemic Events (HE) | Documented Symptomatic HE Rate | 9.62 Events/Participant/Year | Standard Deviation 17.72 |
| Insulin Glargine | Rate of Hypoglycemic Events (HE) | Severe HE Rate | 0.09 Events/Participant/Year | Standard Deviation 0.37 |
| Insulin Glargine | Rate of Hypoglycemic Events (HE) | Nocturnal HE Rate | 2.48 Events/Participant/Year | Standard Deviation 5.1 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events (HE) | Nocturnal HE Rate | 0.76 Events/Participant/Year | Standard Deviation 2.09 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events (HE) | Total HE Rate | 7.59 Events/Participant/Year | Standard Deviation 17.81 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events (HE) | Severe HE Rate | 0.03 Events/Participant/Year | Standard Deviation 0.21 |
| Dulaglutide 0.75 mg | Rate of Hypoglycemic Events (HE) | Documented Symptomatic HE Rate | 4.34 Events/Participant/Year | Standard Deviation 9.3 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events (HE) | Nocturnal HE Rate | 0.70 Events/Participant/Year | Standard Deviation 2.29 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events (HE) | Documented Symptomatic HE Rate | 4.44 Events/Participant/Year | Standard Deviation 12.23 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events (HE) | Severe HE Rate | 0.00 Events/Participant/Year | Standard Deviation 0 |
| Dulaglutide 1.5 mg | Rate of Hypoglycemic Events (HE) | Total HE Rate | 5.82 Events/Participant/Year | Standard Deviation 13.7 |