NCT07096063

Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 887,132 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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. It is intended to assess the comparative effectiveness of 1. Tirzepatide vs dulaglutide, 2. Semaglutide vs sitagliptin, 3. Tirzepatide vs semaglutide on cardiovascular outcomes in individuals typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes (T2DM) and overweight but might not meet the eligibility criteria of pivotal RCTs for each drug (SUSTAIN-6 and SURPASS-CVOT trials), used to support regulatory approval in patients at cardiovascular risk.Although many features of the target trials 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 three database studies will be new-user active-comparative studies, conducted using 3 national United States claims databases, where investigators compare the effect of semaglutide vs sitagliptin (used as an active comparator placebo proxy), tirzepatide vs dulaglutide, and 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.

Conditions

• Type 2 Diabetes
• Overweight
• Cardiovascular (CV) Risk

Interventions

Type	Name	Description
DRUG	Tirzepatide	New use of tirzepatide dispensing claim is used as the exposure.
DRUG	Dulaglutide	New use of dulaglutide dispensing claim is used as the comparator.
DRUG	Semaglutide	New use of semaglutide dispensing claim is used as the exposure/comparator.
DRUG	Sitagliptin	New use of sitagliptin dispensing claim is used as the comparator.

Timeline

• Start date: 2024-10-01
• Primary completion: 2025-07-15
• Completion: 2025-07-15
• First posted: 2025-07-31
• Last updated: 2025-10-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study