Tirzepatide vs Semaglutide in Individuals at Cardiovascular Risk But Without Diabetes.

N/AActive Not RecruitingNCT07619508

Brigham and Women's Hospital100,000 enrolled

Overview

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.

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. It is intended to assess the comparative effectiveness of tirzepatide vs semaglutide on cardiovascular outcomes among patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice. The SELECT trial (NCT03574597) demonstrated that semaglutide reduces major adverse cardiovascular events in individuals with established cardiovascular disease and overweight or obesity but without diabetes. Whether tirzepatide provides similar cardiovascular benefit in patients without diabetes is being evaluated in the ongoing placebo-controlled SURMOUNT-MMO trial (NCT05556512), with results expected in late 2027. Although SURMOUNT-MMO will assess the cardiovascular efficacy of tirzepatide in individuals without diabetes, evidence to inform treatment choices among available incretin-based therapies in clinical practice is urgently needed. Therefore, this study examines the comparative effectiveness of tirzepatide vs semaglutide among patients at cardiovascular risk with overweight or obesity but without diabetes in clinical practice. Although many features of the target trial cannot be directly replicated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected 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 study will be a new-user active-comparative study, conducted using 3 national United States claims databases, where we compare the effect of tirzepatide vs semaglutide on the composite end point of all-cause mortality, myocardial infarction, or stroke. Clinical guidelines during the study period recommended both tirzepatide and semaglutide for the same indications of glucose lowering and weight reduction.

Study Type

OBSERVATIONAL

Enrollment

100,000

Conditions

Obesity Overweight

Interventions

TirzepatideDRUG

Initiation of tirzepatide described in electronic health records is used as the exposure.

SemaglutideDRUG

Initiation of injectable semaglutide described in electronic health records is used as the reference.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Study period: Optum: Eligible cohort entry period between May 13, 2022 to November 30, 2025. MarketScan: Eligible cohort entry period between May 13, 2022 to September 30, 2023. Medicare: Eligible cohort entry period between May 13, 2022 to September 30, 2024. Inclusion Criteria: * Men or women aged 18 years or older * History of myocardial infarction, stroke, any surgical or percutaneous revascularization procedure * Use of antihypertensive or lipid-lowering drugs * Coronary, carotid, or peripheral artery disease * BMI greater than or equal to 25.0 mg/m2 Exclusion Criteria: * Medullary thyroid carcinoma * MEN syndrome type 2 * Malignancy * Type 1 diabetes * Type 2 diabetes * Secondary diabetes * End-stage renal disease or dialysis * Pregnancy * History of bariatric surgery * Prior use of pramlintide or any GLP-1-RA, except tirzepatide or semaglutide * Cardiovascular event or intervention in the last 7 days

Locations (1)

Brigham and Women's Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Composite of all-cause mortality, myocardial infarction, or stroke.

To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the composite of death, myocardial infarction, or stroke in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.

Time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA

Secondary Outcomes

Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke

To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the individual components of the primary endpoint, i.e., death, myocardial infarction, or stroke in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.

Composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure

To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.

Hospitalization for heart failure

Data from ClinicalTrials.gov

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