NCT07619508·Not applicable·OBSERVATIONAL

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

Tirzepatide Semaglutide Glucagon Weight loss Completed

Status

Completed

Phase

Not applicable

Enrollment

100,000

Locations

1

Results

Not posted

Publications

0

Study summary

What the protocol is testing.

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.

Full detailed description

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.

Interventions

Treatment arms and agents.

DRUG

Tirzepatide

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

DRUG

Semaglutide

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

Timeline

From registration to results.

First posted
Jun 2, 2026
Study start
Feb 10, 2026
Primary completion
Jun 1, 2026
Study completion
Jun 1, 2026
Results posted
Not reported
Registry updated
Jul 9, 2026

Outcomes