AWARD-7: A Study Comparing Dulaglutide With Insulin Glargine on Glycemic Control in Participants With Type 2 Diabetes (T2D) and Moderate or Severe Chronic Kidney Disease (CKD)
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01621178
Collaborator
(none)
577
89
3
53
6.5
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
577 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
Dulaglutide dose was blinded to participant, care provider, investigator and outcomes assessor.
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-Label, Parallel-Arm Study Comparing the Effect of Once-weekly Dulaglutide With Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes and Moderate or Severe Chronic Kidney Disease
Study Start Date
:
Jul 1, 2012
Actual Primary Completion Date
:
Jun 1, 2016
Actual Study Completion Date
:
Dec 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Insulin glargine Insulin glargine was administered subcutaneously (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. |
Drug: Insulin glargine
Administered SC
Drug: Insulin lispro
Administered SC
|
| Experimental: 0.75 mg Dulaglutide 0.75 milligram (mg) of dulaglutide was 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. |
Drug: Dulaglutide
Administered SC
Other Names:
Drug: Insulin lispro
Administered SC
|
| Experimental: 1.5 mg Dulaglutide 1.5 mg of dulaglutide was 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. |
Drug: Dulaglutide
Administered SC
Other Names:
Drug: Insulin lispro
Administered SC
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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.
- 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.
- 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.
- Percentage of Participants With Estimated Average Glucose <154 mg/dL [52 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 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
- Change From Baseline in Body Weight [Baseline, 52 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 52 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 52 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 (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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Extended Arm Physician, Inc. | Montgomery | Alabama | United States | 36106 |
| 2 | North American Research Institute | Azusa | California | United States | 91702 |
| 3 | Renal Consultants Medical Group | Granada Hills | California | United States | 91344 |
| 4 | Marin Endocrine Associates | Greenbrae | California | United States | 94904 |
| 5 | Academic Medical Research Institute | Los Angeles | California | United States | 90022 |
| 6 | Sutter Gould Medical Foundation | Modesto | California | United States | 95355 |
| 7 | Infosphere | West Hills | California | United States | 91307 |
| 8 | Chase Medical Research, LLC | Waterbury | Connecticut | United States | 06708 |
| 9 | The Center for Diabetes & Endocrine Care | Hollywood | Florida | United States | 33312 |
| 10 | East Coast Clinical Research | Jacksonville | Florida | United States | 32204 |
| 11 | Ocean Blue Medical Research Center, Inc. | Miami Springs | Florida | United States | 33166 |
| 12 | San Marcus Research Clinic, Inc. | Miami | Florida | United States | 33015 |
| 13 | Pharmax Research Clinic | Miami | Florida | United States | 33126 |
| 14 | Avanced Medical and Pain Mangement Research Clinic (AMPM) | Miami | Florida | United States | 33145 |
| 15 | Baptist Diabetes Association | Miami | Florida | United States | 33156 |
| 16 | Suncoast Clinical Research | New Port Richey | Florida | United States | 34652 |
| 17 | Discovery Medical Research Group | Ocala | Florida | United States | 34471 |
| 18 | Suncoast Clinical Research | Palm Harbor | Florida | United States | 34684 |
| 19 | University of Hawaii Clinical Research | Honolulu | Hawaii | United States | 96813 |
| 20 | Boise Kidney & Hypertension Institute | Caldwell | Idaho | United States | 83605 |
| 21 | Pacific Renal Research Institute | Meridian | Idaho | United States | 83642 |
| 22 | Cotton O'Neil Clinic | Topeka | Kansas | United States | 66606 |
| 23 | Univ of Kansas Schl of Medicine , Wichita | Wichita | Kansas | United States | 67214 |
| 24 | Penobscot Bay Medical Center | Rockport | Maine | United States | 04854 |
| 25 | Nebraska Nephrology Research Institute, LLC | Lincoln | Nebraska | United States | 68510 |
| 26 | Endocrine Group, LLP | Albany | New York | United States | 12206 |
| 27 | Erie County Medical Center State University | Buffalo | New York | United States | 14215 |
| 28 | Institute for clinical studies | Rosedale | New York | United States | 11422 |
| 29 | Endocrine Associates of Long Island, PC | Smithtown | New York | United States | 11787 |
| 30 | Carolina Clinical Trials LLC | Concord | North Carolina | United States | 28025 |
| 31 | Physicians East | Greenville | North Carolina | United States | 27834 |
| 32 | Diabetes & Endocrinology Consultants PC | Morehead City | North Carolina | United States | 28557 |
| 33 | Boice Willis Clinic, PA | Rocky Mount | North Carolina | United States | 27804 |
| 34 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
| 35 | Partners in Nephrology & Endocrinology | Pittsburgh | Pennsylvania | United States | 15224 |
| 36 | South Carolina Nephrology and Hypertension Center, Inc. | Orangeburg | South Carolina | United States | 29118 |
| 37 | Carolina Diabetes & Kidney Ctr. Sumter Medical Specialist | Sumter | South Carolina | United States | 29150 |
| 38 | Southeast Renal Research Institute | Chattanooga | Tennessee | United States | 37408 |
| 39 | Knoxville Kidney Center, PLLC | Knoxville | Tennessee | United States | 37923 |
| 40 | Center For Clinical Research | Austin | Texas | United States | 78758 |
| 41 | Endocrine Associates of Dallas | Dallas | Texas | United States | 75231 |
| 42 | Office of Dr. Sergio Rovner | El Paso | Texas | United States | 79925 |
| 43 | Endocrine Associates, LLC | Houston | Texas | United States | 77004 |
| 44 | Juno Research | Houston | Texas | United States | 77036 |
| 45 | The Endocrine Center | Houston | Texas | United States | 77079 |
| 46 | San Antonio Kidney Disease Center Physicians Group | San Antonio | Texas | United States | 78229 |
| 47 | Providence Health & Services | Spokane | Washington | United States | 99204 |
| 48 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Belem | Brazil | 66073-000 | |
| 49 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Curitiba | Brazil | 80240-000 | |
| 50 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Juiz De Fora | Brazil | 36036-330 | |
| 51 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Passo Fundo | Brazil | 99010-080 | |
| 52 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Porto Alegre | Brazil | 90610000 | |
| 53 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Santa Catarina | Brazil | 89227680 | |
| 54 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | São Paulo | Brazil | 04025-011 | |
| 55 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Baja | Hungary | 6500 | |
| 56 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Budapest | Hungary | 1036 | |
| 57 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Esztergom | Hungary | 2500 | |
| 58 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kaposvar | Hungary | 7400 | |
| 59 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kecskemet | Hungary | 6000 | |
| 60 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Pecs | Hungary | 7623 | |
| 61 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Satoraljaujhely | Hungary | H-3980 | |
| 62 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Siofok | Hungary | 8600 | |
| 63 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chihuahua | Mexico | 31000 | |
| 64 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Culiacan | Mexico | 80030 | |
| 65 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Guadalajara | Mexico | 44650 | |
| 66 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mexico City | Mexico | 11850 | |
| 67 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Monterrey | Mexico | 64000 | |
| 68 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Gdansk | Poland | 80-952 | |
| 69 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lodz | Poland | 90302 | |
| 70 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Szczecin | Poland | 70-111 | |
| 71 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Zgierz | Poland | 95-100 | |
| 72 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bacau | Romania | 600114 | |
| 73 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Bucharest | Romania | 020045 | |
| 74 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Deva | Romania | 330084 | |
| 75 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Oradea | Romania | 410167 | |
| 76 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Targu Mures | Romania | 540142 | |
| 77 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Timisoara | Romania | 300125 | |
| 78 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Cape Town | South Africa | 7925 | |
| 79 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Durban | South Africa | 4091 | |
| 80 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Johannesburg | South Africa | 2198 | |
| 81 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Somerset West | South Africa | 7130 | |
| 82 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Worcester | South Africa | 6850 | |
| 83 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Barcelona | Spain | 08036 | |
| 84 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Valencia | Spain | 46026 | |
| 85 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dnipropetrovsk | Ukraine | 49005 | |
| 86 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kyiv | Ukraine | 2091 | |
| 87 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Lugansk | Ukraine | 91045 | |
| 88 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Poltava | Ukraine | 36011 | |
| 89 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ternopil | Ukraine | 46002 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01621178
Other Study ID Numbers:
- 13798
- H9X-MC-GBDX
- 2012-000829-44
First Posted:
Jun 18, 2012
Last Update Posted:
Sep 19, 2019
Last Verified:
Sep 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Insulin Glargine | 0.75 mg Dulaglutide | 1.5 mg Dulaglutide |
|---|---|---|---|
| Arm/Group Description | Insulin glargine was administered subcutaneously (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. | 0.75 milligram (mg) of dulaglutide was 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. | 1.5 mg of dulaglutide was 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. |
| Period Title: Overall Study | |||
| STARTED | 194 | 190 | 193 |
| Received at Least One Dose of Study Drug | 194 | 190 | 192 |
| Modified Intent to Treat Population | 186 | 180 | 183 |
| COMPLETED | 163 | 160 | 157 |
| NOT COMPLETED | 31 | 30 | 36 |
Baseline Characteristics
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 194 | 190 | 192 | 576 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
64.3
(8.41)
|
64.7
(8.61)
|
64.7
(8.83)
|
64.6
(8.60)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
101
52.1%
|
86
45.3%
|
88
45.8%
|
275
47.7%
|
| Male |
93
47.9%
|
104
54.7%
|
104
54.2%
|
301
52.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
79
40.7%
|
75
39.5%
|
78
40.6%
|
232
40.3%
|
| Not Hispanic or Latino |
115
59.3%
|
115
60.5%
|
114
59.4%
|
344
59.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
18
9.3%
|
17
8.9%
|
12
6.3%
|
47
8.2%
|
| Asian |
5
2.6%
|
4
2.1%
|
7
3.6%
|
16
2.8%
|
| Native Hawaiian or Other Pacific Islander |
1
0.5%
|
0
0%
|
0
0%
|
1
0.2%
|
| Black or African American |
26
13.4%
|
36
18.9%
|
26
13.5%
|
88
15.3%
|
| White |
137
70.6%
|
122
64.2%
|
134
69.8%
|
393
68.2%
|
| More than one race |
6
3.1%
|
7
3.7%
|
10
5.2%
|
23
4%
|
| Unknown or Not Reported |
1
0.5%
|
4
2.1%
|
3
1.6%
|
8
1.4%
|
| Region of Enrollment (Count of Participants) | ||||
| Romania |
14
7.2%
|
9
4.7%
|
14
7.3%
|
37
6.4%
|
| Hungary |
22
11.3%
|
19
10%
|
14
7.3%
|
55
9.5%
|
| United States |
61
31.4%
|
59
31.1%
|
62
32.3%
|
182
31.6%
|
| Ukraine |
17
8.8%
|
11
5.8%
|
12
6.3%
|
40
6.9%
|
| Brazil |
44
22.7%
|
47
24.7%
|
50
26%
|
141
24.5%
|
| Poland |
1
0.5%
|
2
1.1%
|
2
1%
|
5
0.9%
|
| Mexico |
19
9.8%
|
19
10%
|
15
7.8%
|
53
9.2%
|
| South Africa |
14
7.2%
|
20
10.5%
|
17
8.9%
|
51
8.9%
|
| Spain |
2
1%
|
4
2.1%
|
6
3.1%
|
12
2.1%
|
| Body Weight (kilogram (kg)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kilogram (kg)] |
88.20
(18.488)
|
90.88
(18.301)
|
88.14
(16.015)
|
89.06
(17.653)
|
| Body Mass Index (BMI) (kilogram/square meter (kg/m^2)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kilogram/square meter (kg/m^2)] |
32.39
(5.324)
|
33.00
(5.546)
|
32.11
(4.841)
|
32.50
(5.248)
|
| Hemoglobin A1C (HbA1c) at Baseline (Percentage of HbA1c) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Percentage of HbA1c] |
8.56
(0.966)
|
8.57
(1.088)
|
8.59
(0.860)
|
8.57
(0.973)
|
| Duration of Diabetes (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
18.71
(8.742)
|
17.95
(8.788)
|
17.57
(8.722)
|
18.08
(8.748)
|
| Duration of Chronic Kidney Disease (CKD) Stage 3 or Higher (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
3.47
(3.998)
|
4.03
(4.854)
|
4.18
(5.632)
|
3.89
(4.872)
|
| Estimated Glomerular Filtration Rate (eGFR) (milliliter/minute/1.73 square meter) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [milliliter/minute/1.73 square meter] |
38.5
(12.99)
|
38.3
(12.31)
|
38.1
(13.24)
|
38.3
(12.83)
|
Outcome Measures
| Title | Change From Baseline in Hemoglobin A1c (HbA1c) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | Insulin glargine was administered subcutaneous (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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 175 | 149 | 138 |
| Least Squares Mean (Standard Error) [percentage of HbA1c] |
-1.13
(0.12)
|
-1.12
(0.12)
|
-1.19
(0.13)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Glargine, Dulaglutide 1.5 mg |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-Inferiority to Glargine with a 0.4% margin | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.26 to 0.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Insulin Glargine, Dulaglutide 0.75 mg |
|---|---|---|
| Comments | Week 26 | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-Inferiority to Glargine with a 0.4% margin | |
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Mixed Models Analysis | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.18 to 0.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Whose HbA1c Was <7.0% |
|---|---|
| Description | Percentage of participants whose HbA1c was <7.0% based on last observation carried forward (LOCF). |
| Time Frame | 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 182 | 164 | 152 |
| Number [percentage of participants] |
34.6
17.8%
|
31.7
16.7%
|
37.5
19.5%
|
| Title | Percentage of Participants Whose HbA1c Was <8.0% |
|---|---|
| Description | Percentage of Participants whose HbA1c was <8.0% based on last observation carried forward (LOCF). |
| Time Frame | 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 182 | 164 | 152 |
| Number [percentage of participants] |
75.3
38.8%
|
72.6
38.2%
|
78.3
40.8%
|
| Title | Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 128 | 107 | 102 |
| Least Squares Mean (Standard Error) [milligrams/deciliter (mg/dL)] |
-37.6
(3.41)
|
-31.7
(3.53)
|
-33.7
(3.77)
|
| Title | Change From Baseline in Fasting Glucose (FG) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 162 | 145 | 132 |
| Least Squares Mean (Standard Deviation) [milligram/deciliter (mg/dL)] |
-19.1
(6.00)
|
17.7
(6.14)
|
23.1
(6.50)
|
| Title | Change From Baseline in Mean Daily Insulin Lispro Dose |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 177 | 154 | 141 |
| Least Squares Mean (Standard Error) [Units/day (U/day)] |
16.64
(2.76)
|
26.16
(2.80)
|
18.12
(3.00)
|
| Title | Percentage of Participants With Estimated Average Glucose <154 mg/dL |
|---|---|
| Description | Percentage of Participants With Estimated Average Glucose <154 milligram/deciliter (mg/dL) was based on last observation carried forward (LOCF). |
| Time Frame | 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 134 | 118 | 110 |
| Number [percentage of participants] |
64.9
33.5%
|
52.5
27.6%
|
56.4
29.4%
|
| Title | Change From Baseline in Serum Creatinine (sCr) |
|---|---|
| Description | Change from baseline in serum creatinine (sCr) levels after treatment. |
| Time Frame | Baseline, 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline sCr data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 176 | 169 | 163 |
| Median (Inter-Quartile Range) [mg/dL] |
0.10
|
0.02
|
0.04
|
| Title | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) |
|---|---|
| Description | The change in estimated glomerular filtration rate (eGFR) by using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. |
| Time Frame | Baseline, 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline eGFR data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 176 | 169 | 163 |
| Median (Inter-Quartile Range) [milliliter/minute/1.73m2 (mL/min/1.73m2)] |
-2.5
|
-1.0
|
-1.0
|
| Title | Change From Baseline in Estimated Creatinine Clearance (eCrCl) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline eCrCl data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 176 | 169 | 163 |
| Median (Inter-Quartile Range) [milliliter/minute (ml/min)] |
-2.0
|
-1.0
|
-0.5
|
| Title | Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR) |
|---|---|
| Description | The change from baseline in Urinary Albumin to Creatinine Ratio (UACR). |
| Time Frame | Baseline, 26 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline UACR data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 181 | 175 | 175 |
| Median (Inter-Quartile Range) [gram/kilogram (g/kg)] |
-1.3
|
-11.1
|
-10.2
|
| Title | Change From Baseline in Body Weight |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 175 | 151 | 140 |
| Least Squares Mean (Standard Error) [kilogram (kg)] |
1.11
(0.346)
|
-2.02
(0.357)
|
-2.81
(0.374)
|
| Title | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 194 | 189 | 190 |
| Total Hypo |
71.6
36.9%
|
50.8
26.7%
|
43.2
22.5%
|
| Documented Symptomatic Hypo |
60.3
31.1%
|
40.7
21.4%
|
31.6
16.5%
|
| Severe Hypo |
4.1
2.1%
|
1.1
0.6%
|
0
0%
|
| Nocturnal Hypo |
38.1
19.6%
|
15.9
8.4%
|
13.2
6.9%
|
| Title | Rate of Hypoglycemic Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | Insulin glargine administered SC to be given at bedtime per sliding scale. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day. | 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. | 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. |
| Measure Participants | 194 | 189 | 190 |
| Total HE Rate |
17.07
(27.70)
|
7.76
(20.39)
|
5.45
(12.54)
|
| Documented Symptomatic HE Rate |
11.34
(22.04)
|
4.86
(13.37)
|
4.19
(11.58)
|
| Severe HE Rate |
0.10
(0.56)
|
0.03
(0.31)
|
0.00
(0.00)
|
| Nocturnal HE Rate |
3.06
(7.26)
|
0.73
(2.25)
|
0.63
(2.26)
|
| Title | Change From Baseline in HbA1c |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. |
| Measure Participants | 153 | 132 | 130 |
| Least Squares Mean (Standard Error) [percentage of HbA1c] |
-1.00
(0.12)
|
-1.10
(0.12)
|
-1.10
(0.13)
|
| Title | Percentage of Participants Whose HbA1c is <7.0% |
|---|---|
| Description | Percentage of participants whose HbA1c was <7.0% based on last observation carried forward (LOCF). |
| Time Frame | 52 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 182 | 164 | 152 |
| Number [percentage of participants] |
29.1
15%
|
33.5
17.6%
|
32.9
17.1%
|
| Title | Percentage of Participants Whose HbA1c is <8.0% |
|---|---|
| Description | Percentage of participants whose HbA1c was <8.0% based on last observation carried forward (LOCF). |
| Time Frame | 52 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 182 | 164 | 152 |
| Number [percentage of participants] |
70.3
36.2%
|
69.5
36.6%
|
69.1
36%
|
| Title | Change From Baseline in 8-Point SMPG |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 118 | 96 | 102 |
| Least Squares Mean (Standard Error) [mg/dL] |
-40.5
(3.59)
|
-30.0
(3.75)
|
-27.2
(3.93)
|
| Title | Change From Baseline in FG |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 152 | 132 | 131 |
| Least Squares Mean (Standard Error) [mg/dL] |
-6.4
(6.38)
|
20.8
(6.58)
|
28.3
(6.87)
|
| Title | Change in Mean Daily Insulin Lispro Dose |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 159 | 140 | 132 |
| Least Squares Mean (Standard Error) [U/day] |
16.84
(2.87)
|
27.46
(2.93)
|
20.05
(3.13)
|
| Title | Percentage of Participants With Estimated Average Glucose <154 mg/dL |
|---|---|
| Description | Percentage of Participants With Estimated Average Glucose <154 milligram/deciliter (mg/dL) was based on last observation carried forward (LOCF). |
| Time Frame | 52 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 137 | 122 | 116 |
| Number [percentage of participants] |
73.7
38%
|
57.4
30.2%
|
50.9
26.5%
|
| Title | Change From Baseline in sCr |
|---|---|
| Description | Change from baseline in sCr levels after treatment. |
| Time Frame | Baseline, 52 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline sCr data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 164 | 160 | 157 |
| Median (Inter-Quartile Range) [mg/dL] |
0.12
|
0.04
|
0.07
|
| Title | Change From Baseline in eGFR |
|---|---|
| Description | The change in eGFR by using CKD-EPI equation. |
| Time Frame | Baseline, 52 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had evaluable baseline and post baseline eGFR data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 164 | 160 | 157 |
| Median (Inter-Quartile Range) [mL/min/1.73m2] |
-3.3
|
-1.5
|
-2.0
|
| Title | Change From Baseline in eCrCl |
|---|---|
| Description | eCrCl was calculated by Cockcroft-Gault [Cockcroft and Gault 1976] equation using baseline estimated lean body weight. |
| Time Frame | Baseline, 52 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline eCrCl data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 164 | 160 | 157 |
| Median (Inter-Quartile Range) [mL/min] |
-2.5
|
-1.3
|
-1.5
|
| Title | Change From Baseline in UACR |
|---|---|
| Description | The change from baseline in UACR |
| Time Frame | Baseline, 52 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received one dose of study drug and had evaluable baseline and post-baseline UACR data. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 165 | 162 | 159 |
| Median (Inter-Quartile Range) [g/kg] |
3.5
|
-3.0
|
-11.5
|
| Title | Change From Baseline in Body Weight |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 158 | 137 | 132 |
| Least Squares Mean (Standard Error) [kg] |
1.57
(0.429)
|
-1.71
(0.448)
|
-2.66
(0.467)
|
| Title | Percentage of Participants With Self-Reported Hypoglycemic Events (HE) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 194 | 189 | 190 |
| Total Hypo |
74.7
38.5%
|
59.8
31.5%
|
50.0
26%
|
| Documented Symptomatic Hypo |
63.4
32.7%
|
48.1
25.3%
|
40.5
21.1%
|
| Severe Hypo |
6.7
3.5%
|
2.6
1.4%
|
0
0%
|
| Nocturnal Hypo |
47.9
24.7%
|
23.8
12.5%
|
20.5
10.7%
|
| Title | Rate of Hypoglycemic Events (HE) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 194 | 189 | 190 |
| Total HE Rate |
14.36
(22.20)
|
7.59
(17.81)
|
5.82
(13.70)
|
| Documented Symptomatic HE Rate |
9.62
(17.72)
|
4.34
(9.30)
|
4.44
(12.23)
|
| Severe HE Rate |
0.09
(0.37)
|
0.03
(0.21)
|
0.00
(0.00)
|
| Nocturnal HE Rate |
2.48
(5.10)
|
0.76
(2.09)
|
0.70
(2.29)
|
| Title | Participants With Events of Allergic/Hypersensitivity Reactions |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who received at least one dose of study drug. |
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg |
|---|---|---|---|
| Arm/Group Description | 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. | Dulaglutide 0.75 mg was 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. | Dulaglutide 1.5 mg was 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. |
| Measure Participants | 194 | 190 | 192 |
| Angioedema SMQ |
1
0.5%
|
2
1.1%
|
2
1%
|
| Angioedema |
0
0%
|
0
0%
|
1
0.5%
|
| Eyelid edema |
0
0%
|
1
0.5%
|
0
0%
|
| Face edema |
0
0%
|
1
0.5%
|
1
0.5%
|
| Urticaria |
1
0.5%
|
0
0%
|
0
0%
|
| Anaphylactic Reaction SMQ |
1
0.5%
|
0
0%
|
0
0%
|
| Circulatory collapse |
1
0.5%
|
0
0%
|
0
0%
|
| Severe Cutaneous Adverse Reactions SMQ |
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Up To Week 52 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population included those participants who received at least one dose of study drug. | |||||
| Arm/Group Title | Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg | |||
| Arm/Group Description | Insulin glargine administered SC to be given at bedtime per sliding scale. Participants were instructed to administer their titrated prandial insulin lispro dose SC with the three most significant meals of the day. | 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. | 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. | |||
All Cause Mortality |
||||||
| Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 56/194 (28.9%) | 48/190 (25.3%) | 41/192 (21.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Cardiac disorders | ||||||
| Acute coronary syndrome | 2/194 (1%) | 2 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Acute myocardial infarction | 4/194 (2.1%) | 4 | 6/190 (3.2%) | 6 | 0/192 (0%) | 0 |
| Angina pectoris | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Angina unstable | 3/194 (1.5%) | 3 | 2/190 (1.1%) | 2 | 1/192 (0.5%) | 1 |
| Atrial fibrillation | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Cardiac arrest | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Cardiac failure | 1/194 (0.5%) | 1 | 1/190 (0.5%) | 1 | 3/192 (1.6%) | 3 |
| Cardiac failure acute | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Cardiac failure congestive | 2/194 (1%) | 2 | 2/190 (1.1%) | 2 | 2/192 (1%) | 2 |
| Coronary artery disease | 1/194 (0.5%) | 1 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Coronary artery occlusion | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Heart valve incompetence | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Ischaemic cardiomyopathy | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Myocardial infarction | 1/194 (0.5%) | 1 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Myocardial ischaemia | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Palpitations | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Eye disorders | ||||||
| Retinal artery occlusion | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Visual acuity reduced | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 1/192 (0.5%) | 6 |
| Abdominal pain lower | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Colitis ischaemic | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Diarrhoea | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 2/192 (1%) | 2 |
| Gastritis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Nausea | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Pancreatitis acute | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 2/192 (1%) | 2 |
| Vomiting | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 1/192 (0.5%) | 6 |
| General disorders | ||||||
| Chest pain | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 3/192 (1.6%) | 3 |
| Death | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Ischaemic ulcer | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Non-cardiac chest pain | 1/194 (0.5%) | 1 | 1/190 (0.5%) | 1 | 2/192 (1%) | 2 |
| Oedema peripheral | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Pacemaker generated arrhythmia | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Pyrexia | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Sudden death | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 0/194 (0%) | 0 | 2/190 (1.1%) | 2 | 0/192 (0%) | 0 |
| Portal vein thrombosis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Immune system disorders | ||||||
| Drug hypersensitivity | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Infections and infestations | ||||||
| Abdominal abscess | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Appendicitis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Cellulitis | 3/194 (1.5%) | 3 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Clostridium difficile colitis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Diverticulitis | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Gastroenteritis | 1/194 (0.5%) | 1 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Gastroenteritis viral | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 1/192 (0.5%) | 1 |
| Groin abscess | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Localised infection | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Osteomyelitis | 1/194 (0.5%) | 1 | 1/190 (0.5%) | 1 | 1/192 (0.5%) | 1 |
| Pneumonia | 3/194 (1.5%) | 3 | 3/190 (1.6%) | 3 | 0/192 (0%) | 0 |
| Pneumonia haemophilus | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Pneumonia legionella | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Pseudomembranous colitis | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Pyelonephritis | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Sepsis | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 2/192 (1%) | 2 |
| Tonsillitis | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Tracheobronchitis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Urinary tract infection | 3/194 (1.5%) | 3 | 2/190 (1.1%) | 2 | 1/192 (0.5%) | 1 |
| Wound infection | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Accidental overdose | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Ankle fracture | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Concussion | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Fall | 2/194 (1%) | 2 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Foot fracture | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Postpericardiotomy syndrome | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Road traffic accident | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Tendon rupture | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Toxicity to various agents | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Wrist fracture | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Investigations | ||||||
| Blood creatinine increased | 2/194 (1%) | 3 | 3/190 (1.6%) | 3 | 3/192 (1.6%) | 3 |
| Glomerular filtration rate decreased | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Haemoglobin decreased | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Red blood cell sedimentation rate increased | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 2/192 (1%) | 2 |
| Fluid retention | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Hyperglycaemia | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 2/192 (1%) | 2 |
| Hypoglycaemia | 13/194 (6.7%) | 17 | 6/190 (3.2%) | 7 | 1/192 (0.5%) | 1 |
| Hyponatraemia | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| Musculoskeletal chest pain | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Osteoarthritis | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Pain in extremity | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Rhabdomyolysis | 0/194 (0%) | 0 | 2/190 (1.1%) | 2 | 1/192 (0.5%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Bladder neoplasm | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Gastric cancer | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Nervous system disorders | ||||||
| Carotid artery stenosis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Cerebrovascular accident | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 2/192 (1%) | 2 |
| Cervical radiculopathy | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Iiird nerve paralysis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Ischaemic stroke | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 2/192 (1%) | 2 |
| Myoclonus | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Presyncope | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Sciatica | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Syncope | 1/194 (0.5%) | 1 | 1/190 (0.5%) | 1 | 1/192 (0.5%) | 1 |
| Transient ischaemic attack | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 2/194 (1%) | 2 | 5/190 (2.6%) | 5 | 3/192 (1.6%) | 3 |
| Chronic kidney disease | 2/194 (1%) | 4 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| End stage renal disease | 2/194 (1%) | 2 | 2/190 (1.1%) | 2 | 2/192 (1%) | 2 |
| Haematuria | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Prerenal failure | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Renal injury | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Tubulointerstitial nephritis | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Urethral haemorrhage | 1/194 (0.5%) | 2 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Colpocele | 1/101 (1%) | 1 | 0/86 (0%) | 0 | 0/88 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute pulmonary oedema | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Aspiration | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Dyspnoea | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Epistaxis | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Pleural effusion | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Pulmonary embolism | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Respiratory distress | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Respiratory failure | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Diabetic foot | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Skin ulcer | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Vascular disorders | ||||||
| Circulatory collapse | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Deep vein thrombosis | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Hypertension | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Hypertensive crisis | 0/194 (0%) | 0 | 1/190 (0.5%) | 1 | 0/192 (0%) | 0 |
| Hypotension | 1/194 (0.5%) | 1 | 0/190 (0%) | 0 | 0/192 (0%) | 0 |
| Peripheral arterial occlusive disease | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Peripheral ischaemia | 0/194 (0%) | 0 | 0/190 (0%) | 0 | 1/192 (0.5%) | 1 |
| Peripheral vascular disorder | 0/194 (0%) | 0 | 2/190 (1.1%) | 2 | 0/192 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Insulin Glargine | Dulaglutide 0.75 mg | Dulaglutide 1.5 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 130/194 (67%) | 134/190 (70.5%) | 144/192 (75%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 10/194 (5.2%) | 10 | 3/190 (1.6%) | 3 | 5/192 (2.6%) | 5 |
| Gastrointestinal disorders | ||||||
| Constipation | 6/194 (3.1%) | 6 | 10/190 (5.3%) | 10 | 12/192 (6.3%) | 13 |
| Diarrhoea | 14/194 (7.2%) | 17 | 30/190 (15.8%) | 37 | 31/192 (16.1%) | 49 |
| Nausea | 9/194 (4.6%) | 9 | 27/190 (14.2%) | 38 | 38/192 (19.8%) | 52 |
| Vomiting | 9/194 (4.6%) | 9 | 16/190 (8.4%) | 22 | 26/192 (13.5%) | 42 |
| General disorders | ||||||
| Oedema peripheral | 15/194 (7.7%) | 16 | 12/190 (6.3%) | 13 | 10/192 (5.2%) | 10 |
| Infections and infestations | ||||||
| Influenza | 10/194 (5.2%) | 10 | 15/190 (7.9%) | 18 | 12/192 (6.3%) | 12 |
| Nasopharyngitis | 12/194 (6.2%) | 15 | 9/190 (4.7%) | 12 | 11/192 (5.7%) | 12 |
| Sinusitis | 11/194 (5.7%) | 13 | 4/190 (2.1%) | 4 | 2/192 (1%) | 2 |
| Upper respiratory tract infection | 20/194 (10.3%) | 26 | 13/190 (6.8%) | 15 | 8/192 (4.2%) | 9 |
| Urinary tract infection | 19/194 (9.8%) | 25 | 10/190 (5.3%) | 12 | 13/192 (6.8%) | 16 |
| Investigations | ||||||
| Blood creatinine increased | 90/194 (46.4%) | 124 | 71/190 (37.4%) | 102 | 74/192 (38.5%) | 106 |
| Glomerular filtration rate decreased | 26/194 (13.4%) | 29 | 20/190 (10.5%) | 25 | 17/192 (8.9%) | 22 |
| Weight increased | 16/194 (8.2%) | 18 | 9/190 (4.7%) | 9 | 9/192 (4.7%) | 10 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/194 (1.5%) | 3 | 5/190 (2.6%) | 6 | 11/192 (5.7%) | 11 |
| Hyperkalaemia | 13/194 (6.7%) | 15 | 8/190 (4.2%) | 10 | 12/192 (6.3%) | 14 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 7/194 (3.6%) | 8 | 8/190 (4.2%) | 8 | 10/192 (5.2%) | 10 |
| Nervous system disorders | ||||||
| Dizziness | 10/194 (5.2%) | 12 | 11/190 (5.8%) | 12 | 8/192 (4.2%) | 11 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 15/194 (7.7%) | 17 | 7/190 (3.7%) | 7 | 7/192 (3.6%) | 8 |
| Vascular disorders | ||||||
| Hypertension | 20/194 (10.3%) | 20 | 13/190 (6.8%) | 13 | 14/192 (7.3%) | 14 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01621178
Other Study ID Numbers:
- 13798
- H9X-MC-GBDX
- 2012-000829-44
First Posted:
Jun 18, 2012
Last Update Posted:
Sep 19, 2019
Last Verified:
Sep 1, 2019