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)
- Conditions
- Type 2 DiabetesChronic Kidney Disease
- Interventions
- Registration Number
- NCT01621178
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 577
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1.5 mg Dulaglutide Insulin lispro 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. Insulin glargine 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. Insulin glargine Insulin lispro 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 mg Dulaglutide 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. 0.75 mg Dulaglutide Insulin lispro 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 Dulaglutide 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 Serum Creatinine (sCr) Baseline, 26 Weeks Change from baseline in serum creatinine (sCr) levels after treatment.
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.
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
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).
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 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 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 Urinary Albumin to Creatinine Ratio (UACR) Baseline, 26 Weeks The change from baseline in Urinary Albumin to Creatinine Ratio (UACR).
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 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).
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 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.
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.
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 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 in Mean Daily Insulin Lispro Dose Baseline, 52 Weeks The mean daily insulin was based on a 4-week interval prior to week 52 assessments. LS means were calculated using a REML based mixed-effects model for repeated measures (MMRM) with the change in mean daily insulin as the dependent variable and treatment, MA-region, Baseline HbA1c, baseline mean daily insulin, baseline CKD Severity, week, treatment\*week, log baseline eGFR (within CKD severity), and participant was the random effect. Covariance structure = Unstructured.
Change From Baseline in eGFR Baseline, 52 Weeks The change in eGFR by using CKD-EPI equation.
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.
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 sCr Baseline, 52 Weeks Change from baseline in sCr levels after treatment.
Trial Locations
- Locations (47)
Academic Medical Research Institute
🇺🇸Los Angeles, California, United States
Extended Arm Physician, Inc.
🇺🇸Montgomery, Alabama, United States
Infosphere
🇺🇸West Hills, California, United States
Discovery Medical Research Group
🇺🇸Ocala, Florida, United States
Boise Kidney & Hypertension Institute
🇺🇸Caldwell, Idaho, United States
East Coast Clinical Research
🇺🇸Jacksonville, Florida, United States
Office of Dr. Sergio Rovner
🇺🇸El Paso, Texas, United States
Erie County Medical Center State University
🇺🇸Buffalo, New York, United States
The Center for Diabetes & Endocrine Care
🇺🇸Hollywood, Florida, United States
Renal Consultants Medical Group
🇺🇸Granada Hills, California, United States
Pacific Renal Research Institute
🇺🇸Meridian, Idaho, United States
Physicians East
🇺🇸Greenville, North Carolina, United States
Endocrine Group, LLP
🇺🇸Albany, New York, United States
Institute for clinical studies
🇺🇸Rosedale, New York, United States
Penobscot Bay Medical Center
🇺🇸Rockport, Maine, United States
Providence Health & Services
🇺🇸Spokane, Washington, United States
Partners in Nephrology & Endocrinology
🇺🇸Pittsburgh, Pennsylvania, United States
Endocrine Associates, LLC
🇺🇸Houston, Texas, United States
Juno Research
🇺🇸Houston, Texas, United States
The Endocrine Center
🇺🇸Houston, Texas, United States
Marin Endocrine Associates
🇺🇸Greenbrae, California, United States
North American Research Institute
🇺🇸Azusa, California, United States
Ocean Blue Medical Research Center, Inc.
🇺🇸Miami Springs, Florida, United States
Suncoast Clinical Research
🇺🇸Palm Harbor, Florida, United States
Endocrine Associates of Long Island, PC
🇺🇸Smithtown, New York, United States
Carolina Diabetes & Kidney Ctr. Sumter Medical Specialist
🇺🇸Sumter, South Carolina, United States
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
San Marcus Research Clinic, Inc.
🇺🇸Miami, Florida, United States
Pharmax Research Clinic
🇺🇸Miami, Florida, United States
Avanced Medical and Pain Mangement Research Clinic (AMPM)
🇺🇸Miami, Florida, United States
Baptist Diabetes Association
🇺🇸Miami, Florida, United States
Univ of Kansas Schl of Medicine , Wichita
🇺🇸Wichita, Kansas, United States
Cotton O'Neil Clinic
🇺🇸Topeka, Kansas, United States
San Antonio Kidney Disease Center Physicians Group
🇺🇸San Antonio, Texas, United States
Sutter Gould Medical Foundation
🇺🇸Modesto, California, United States
Carolina Clinical Trials LLC
🇺🇸Concord, North Carolina, United States
Endocrine Associates of Dallas
🇺🇸Dallas, Texas, United States
Diabetes & Endocrinology Consultants PC
🇺🇸Morehead City, North Carolina, United States
Boice Willis Clinic, PA
🇺🇸Rocky Mount, North Carolina, United States
Knoxville Kidney Center, PLLC
🇺🇸Knoxville, Tennessee, United States
Chase Medical Research, LLC
🇺🇸Waterbury, Connecticut, United States
Nebraska Nephrology Research Institute, LLC
🇺🇸Lincoln, Nebraska, United States
Southeast Renal Research Institute
🇺🇸Chattanooga, Tennessee, United States
South Carolina Nephrology and Hypertension Center, Inc.
🇺🇸Orangeburg, South Carolina, United States
University of Hawaii Clinical Research
🇺🇸Honolulu, Hawaii, United States
Center For Clinical Research
🇺🇸Austin, Texas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States