Comparative Effectiveness of Dulaglutide, Semaglutide, and Tirzepatide in Preventing Cardiovascular Events in Patients With Type 2 Diabetes and Obesity With or Without Atherosclerotic Cardiovascular Disease.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60,000
- 试验地点
- 1
- 主要终点
- Composite of myocardial infarction, stroke, or all-cause mortality.
研究概览
简要总结
Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.
详细描述
This is a non-randomized, non-interventional study that is part of the Randomized Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology (RCT-DUPLICATE) initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. Randomized controlled trials (RCTs) have demonstrated cardiovascular benefits of the modern incretin therapies semaglutide and tirzepatide in selected populations. SUSTAIN-6 (NCT01720446) and SURPASS-CVOT (NCT04255433) showed reductions in cardiovascular events with semaglutide and tirzepatide among patients with T2DM at high cardiovascular risk, findings that were also replicated in clinical practice settings (NCT06659744, NCT07088718). The REWIND trial (NCT01394952) demonstrated similar cardiovascular efficacy for dulaglutide and suggested benefit in both patients with and without prior cardiovascular disease.4 These findings raise the broader question of whether cardiovascular benefits of modern incretin therapies extend to individuals without established atherosclerotic cardiovascular disease (ASCVD) when used in routine clinical practice.
To address this question, this comparative effectiveness study using a target trial emulation framework will assess the incretin therapies dulaglutide, semaglutide, and tirzepatide vs sitagliptin (used as an active comparator placebo proxy) on major adverse cardiovascular events (MACE) among individuals with type 2 diabetes (T2DM) and overweight with or without ASCVD.
Although many features of the target trial cannot be directly replicated in healthcare claims, measurements of key design features, including outcomes, exposures, and inclusion/exclusion criteria, were designed to proxy those features from the target trial. Randomization cannot be achieved in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice.
The database analyses will be new-user active-comparative studies, conducted using 3 national United States claims databases, where we compare the effect of dulaglutide, semaglutide, and tirzepatide vs sitagliptin on preventing atherosclerotic cardiovascular events.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
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
- •The database analyses will be new-user active-comparative studies, conducted using 3 national United States claims databases, where we compare the effect of dulaglutide, semaglutide, and tirzepatide vs sitagliptin on preventing atherosclerotic cardiovascular events.
- •Optum: Eligible cohort entry period from September 18, 2014 to August 31,
- •Marketscan: Eligible cohort entry from October 1, 2016 to October 31,
- •Medicare: Eligible cohort entry from September 18, 2014 to October 31,
- •POPULATION WITH ASCVD
- •Inclusion Criteria:
- •History of ASCVD (defined as MI, ACS, stable/unstable angina surgical or percutaneous coronary/other arterial revascularization procedure, ischemic stroke, TIA, aortic aneurysm, peripheral artery disease)
- •BMI >= 25.0kg/m2
- •Type 2 Diabetes
排除标准
- •Medullary thyroid carcinoma
- •MEN syndrome type 2
- •Malignancy
- •Type 1 diabetes or secondary diabetes
- •End-stage renal disease or dialysis
- •Uncontrolled diabetic retinopathy or maculopathy
- •Pregnancy
- •Bariatric surgery
- •Prior use of pramlintide, or any GLP-1RA except injectable semaglutide/tirzepatide/dulaglutide, or any DPP4i except sitagliptin
- •CV-event or intervention
- •Concurrent use of both study drugs
- •POPULATION WITHOUT ASCVD
- •Inclusion Criteria:
- •BMI >=25.0kg/m2
- •Type 2 diabetes
- •Exclusion Criteria:
- •History of ASCVD (defined as MI, ACS, stable/unstable angina surgical or percutaneous coronary/other arterial revascularization procedure, ischemic stroke, TIA, aortic aneurysm, peripheral artery disease)
- •Medullary thyroid carcinoma
- •MEN syndrome type 2
- •Malignancy
- •Type 1 diabetes or secondary diabetes
- •End-stage renal disease or dialysis
- •Uncontrolled diabetic retinopathy or maculopathy
- •Pregnancy
- •Bariatric surgery
- •Prior use of pramlintide, or any GLP-1RA except injectable semaglutide/tirzepatide/dulaglutide, or any DPP4i except sitagliptin
- •Concurrent use of both study drugs
研究组 & 干预措施
Initiation of dulaglutide, semaglutide or tirzepatide
Exposure group.
干预措施: Semaglutide (Drug)
Initiation of dulaglutide, semaglutide or tirzepatide
Exposure group.
干预措施: Dulaglutide (Drug)
Initiation of sitagliptin
Reference group.
干预措施: Sitagliptin (Drug)
Initiation of dulaglutide, semaglutide or tirzepatide
Exposure group.
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Composite of myocardial infarction, stroke, or all-cause mortality.
时间窗: Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i
To evaluate the comparative effect of dulaglutide, semaglutide, and tirzepatide vs sitagliptin on the composite of myocardial infarction, stroke, or all-cause mortality in individuals with T2DM and overweight with ASCVD.
Composite of myocardial infarction, or stroke.
时间窗: Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i
To evaluate the comparative effect of dulaglutide, semaglutide, and tirzepatide vs sitagliptin on the composite of myocardial infarction or stroke in individuals with T2DM and overweight with ASCVD.
次要结局
- Myocardial infarction(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Stroke(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- All-cause mortality(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Composite of myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure.(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Unstable angina(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Coronary revascularization(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Heart failure(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Time to first hospitalization for any cause.(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Time to first hospitalization for any cause(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Urinary tract infections(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Serious infections(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
- Gastrointestinal adverse events(Through study completion until first of outcome, disenrollment, end of study period, 365 days after cohort entry, discontinuation (45 days grace and risk window), switch between study arms, nursing home admission, or start of any other GLP-1-RA or DPP4i)
研究者
Shirley Vichy Wang
Associate Professor
Brigham and Women's Hospital