NCT07417618

INcreTin-based thERapies for Cardiovascular Event PrevenTion in Patients With and Without ASCVD (INTERCEPT-ASCVD)

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.

• Status: Active Not Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 60,000 (estimated)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: —

Summary

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.

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. 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).1-3 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.

Conditions

• Type 2 Diabetes
• Overweight
• ASCVD

Interventions

Type	Name	Description
DRUG	Dulaglutide	Initiation of dulaglutide dispensing claim is used as the exposure.
DRUG	Semaglutide	Initiation of semaglutide dispensing claim is used as the exposure.
DRUG	Tirzepatide	Initiation of tirzepatide dispensing claim is used as the exposure.
DRUG	Sitagliptin	Initiation of sitagliptin dispensing claim is used as the reference.

Timeline

• Start date: 2026-01-27
• Primary completion: 2026-03-01
• Completion: 2026-03-01
• First posted: 2026-02-18
• Last updated: 2026-02-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study