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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 577
- 试验地点
- 47
- 主要终点
- Change From Baseline in Hemoglobin A1c (HbA1c)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Dulaglutide dose was blinded to participant, care provider, investigator and outcomes assessor.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Insulin glargine (Drug)
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.
干预措施: Insulin lispro (Drug)
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.
干预措施: Dulaglutide (Drug)
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.
干预措施: Insulin lispro (Drug)
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.
干预措施: Dulaglutide (Drug)
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.
干预措施: Insulin lispro (Drug)
结局指标
主要结局
Change From Baseline in Hemoglobin A1c (HbA1c)
时间窗: 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.
次要结局
- Change From Baseline in Serum Creatinine (sCr)(Baseline, 26 Weeks)
- Rate of Hypoglycemic Events(Baseline through 26 Weeks)
- Participants With Events of Allergic/Hypersensitivity Reactions(Baseline through 52 Weeks)
- Percentage of Participants Whose HbA1c Was <7.0%(26 Weeks)
- Change From Baseline in Fasting Glucose (FG)(Baseline, 26 Weeks)
- Change From Baseline in Estimated Creatinine Clearance (eCrCl)(Baseline, 26 Weeks)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline, 26 Weeks)
- Change From Baseline in Urinary Albumin to Creatinine Ratio (UACR)(Baseline, 26 Weeks)
- Percentage of Participants Whose HbA1c Was <8.0%(26 Weeks)
- Change From Baseline in 8-Point Self-Monitored Plasma Glucose (SMPG)(Baseline, 26 Weeks)
- Change From Baseline in Mean Daily Insulin Lispro Dose(Baseline, 26 Weeks)
- Percentage of Participants Whose HbA1c is <7.0%(52 Weeks)
- Percentage of Participants Whose HbA1c is <8.0%(52 Weeks)
- Percentage of Participants With Estimated Average Glucose <154 mg/dL(52 Weeks)
- Change From Baseline in Body Weight(Baseline, 52 Weeks)
- Percentage of Participants With Self-Reported Hypoglycemic Events (HE)(Baseline through 52 Weeks)
- Change From Baseline in HbA1c(Baseline, 52 Weeks)
- Change From Baseline in FG(Baseline, 52 Weeks)
- Change From Baseline in eCrCl(Baseline, 52 Weeks)
- Change From Baseline in UACR(Baseline, 52 Weeks)
- Change in Mean Daily Insulin Lispro Dose(Baseline, 52 Weeks)
- Change From Baseline in eGFR(Baseline, 52 Weeks)
- Rate of Hypoglycemic Events (HE)(Baseline through 52 Weeks)
- Change From Baseline in 8-Point SMPG(Baseline, 52 Weeks)
- Change From Baseline in sCr(Baseline, 52 Weeks)