A Randomized, Parallel-Arm, Double-Blind Study of Efficacy and Safety of Dulaglutide When Added to SGLT2 Inhibitors in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 424
- 试验地点
- 17
- 主要终点
- Change From Baseline in Hemoglobin A1c (HbA1c) at 24 Weeks (Treatment-regimen Estimand)
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy and safety of the study drug known as dulaglutide when added to sodium-glucose co-transporter 2 (SGLT2) inhibitors in participants with type 2 diabetes mellitus.
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
- Double (Participant, Investigator)
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
- •Have type 2 diabetes mellitus (based on the World Health Organization's [WHO] diagnostic criteria)
- •Have been treated with an SGLT2 inhibitor, with or without metformin, for at least 3 months prior to study entry (minimum required doses for that period for allowed SGLT2 inhibitors: empagliflozin 10 mg, dapagliflozin 5 or 10 mg [per country-specific label], canagliflozin 100 mg); minimum required dose for metformin, if used, is ≥1500 mg/day and must be reached (or highest tolerated dose which is acceptable with documented gastrointestinal [GI] intolerability)
- •Daily doses of all allowed oral antihyperglycemia agent (OAMs) must have been stable for at least 12 weeks (±3 days) prior to randomization (study enrollment); daily doses of SGLT2 inhibitor and metformin, if used, will be considered stable during this period if:
- •all prescribed daily doses were in the range between the minimum required dose and maximum-approved dose per country-specific label; and
- •>90% of prescribed daily doses were equal to the dose at randomization
- •Have HbA1c ≥7.0% and ≤9.5% at study entry and approximately 1 week prior to randomization
- •Have body mass index (BMI) ≤45 kilograms per meter squared (kg/m^2) and agree to not initiate a diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment
排除标准
- •Have type 1 diabetes mellitus
- •Have been treated with any other OAMs (other than SGLT2 inhibitors and metformin), glucagon-like peptide-1 receptor agonist (GLP-1 RA), pramlintide or insulin 3 months prior to study entry, or between study entry and randomization; or initiate metformin between study entry and randomization; short-term use of insulin for acute care (≤14 days) during the 3-month period prior to entry is not exclusionary
- •Have any condition that is a contraindication for use of the GLP-1 RA class or the SGLT2 inhibitor class (per country-specific labels) at study entry or develop such condition between study entry and randomization
- •Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine transaminase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial
- •Had chronic or acute pancreatitis any time prior to study entry
- •Estimated glomerular filtration rate (eGFR) <45 milliliters(mL)/minute/1.73m^2, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, as determined by the central laboratory at study entry and confirmed at lead in
- •Have any self or family history of type 2A or type 2B multiple endocrine neoplasia (MEN 2A or 2B) in the absence of known C-cell hyperplasia (this exclusion includes participants with a family history of MEN 2A or 2B, whose family history for the syndrome is rearranged during transfect [RET]-negative; the only exception for this exclusion will be for participants whose family members with MEN 2A or 2B have a known RET mutation and the potential participant for the study is negative for the RET mutation)
- •Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, carcinoma (including sporadic, familial, or part of MEN 2A or 2B syndrome)
- •Have a serum calcitonin ≥20 picograms/mL as determined by the central laboratory at study entry
研究组 & 干预措施
1.5 mg Dulaglutide
1.5 milligrams (mg) given subcutaneously (SC) once a week for 24 weeks.
干预措施: Dulaglutide (Drug)
1.5 mg Dulaglutide
1.5 milligrams (mg) given subcutaneously (SC) once a week for 24 weeks.
干预措施: SGLT2 inhibitor (Drug)
1.5 mg Dulaglutide
1.5 milligrams (mg) given subcutaneously (SC) once a week for 24 weeks.
干预措施: Metformin (Drug)
0.75 mg Dulaglutide
0.75 mg dulaglutide given SC once a week for 24 weeks.
干预措施: Dulaglutide (Drug)
0.75 mg Dulaglutide
0.75 mg dulaglutide given SC once a week for 24 weeks.
干预措施: SGLT2 inhibitor (Drug)
0.75 mg Dulaglutide
0.75 mg dulaglutide given SC once a week for 24 weeks.
干预措施: Metformin (Drug)
Placebo
Placebo given SC once a week for 24 weeks.
干预措施: Placebo (Drug)
Placebo
Placebo given SC once a week for 24 weeks.
干预措施: SGLT2 inhibitor (Drug)
Placebo
Placebo given SC once a week for 24 weeks.
干预措施: Metformin (Drug)
结局指标
主要结局
Change From Baseline in Hemoglobin A1c (HbA1c) at 24 Weeks (Treatment-regimen Estimand)
时间窗: Baseline, Week 24
Least Squares mean (LS) of the HbA1c change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, treatment-by-visit interactions as fixed effects, and baseline HbA1c as a covariate and participant as a random effect, via a MMRM analysis. The treatment-regimen estimand used all data including post-rescue data and compared the benefit of treatment regimens as they were actually taken.
Change From Baseline in the HbA1c at 24 Weeks (Efficacy Estimand)
时间窗: Baseline, Week 24
LS mean of the HbA1c change from baseline to primary endpoint at week 24 was adjusted by treatment, country, SGLT2 inhibitor dose, metformin use, treatment-by-visit interactions as fixed effects, and baseline HbA1c as a covariate and participant as a random effect, via a MMRM analysis. The efficacy estimand excluded post-rescue data and compared the benefit of randomized treatments when taken as directed without rescue medication.
次要结局
- Change From Baseline in 6-Point Self-Monitored Plasma Glucose (SMPG) Profile at 24 Weeks(Baseline, Week 24)
- Percentage of Participants With HbA1c <7%(24 Weeks)
- Change From Baseline in Body Weight at 24 Weeks(Baseline, Week 24)
- Change From Baseline in Fasting Serum Glucose (Central Laboratory) at 24 Weeks(Baseline, Week 24)
- Change From Baseline in Fasting Glucagon at 24 Weeks(Baseline, Week 24)
- Rate of Hypoglycemic Events Adjusted Per 30 Days(Baseline through 24 Weeks)
- Number of Participants Requiring Rescue Therapy Due to Severe Persistent Hyperglycemia(Baseline through 24 Weeks)
- Number of Participants With Adjudicated Acute Pancreatitis Events(Baseline through 24 Weeks)
- Number of Participants With Adjudicated Cardiovascular (CV) Events(Baseline through 24 Weeks)