Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk

NCT ID: NCT07096063

Last Updated: 2025-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

887132 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-10-01

Study Completion Date

2025-07-15

Brief Summary

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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

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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

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Type 2 Diabetes Overweight Cardiovascular (CV) Risk

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Cohort 1

Tirzepatide vs dulaglutide

Tirzepatide

Intervention Type DRUG

New use of tirzepatide dispensing claim is used as the exposure.

Dulaglutide

Intervention Type DRUG

New use of dulaglutide dispensing claim is used as the comparator.

Cohort 2

Semaglutide vs sitagliptin

Semaglutide

Intervention Type DRUG

New use of semaglutide dispensing claim is used as the exposure/comparator.

Sitagliptin

Intervention Type DRUG

New use of sitagliptin dispensing claim is used as the comparator.

Cohort 3

Tirzepatide vs semaglutide

Tirzepatide

Intervention Type DRUG

New use of tirzepatide dispensing claim is used as the exposure.

Semaglutide

Intervention Type DRUG

New use of semaglutide dispensing claim is used as the exposure/comparator.

Interventions

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Tirzepatide

New use of tirzepatide dispensing claim is used as the exposure.

Intervention Type DRUG

Dulaglutide

New use of dulaglutide dispensing claim is used as the comparator.

Intervention Type DRUG

Semaglutide

New use of semaglutide dispensing claim is used as the exposure/comparator.

Intervention Type DRUG

Sitagliptin

New use of sitagliptin dispensing claim is used as the comparator.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* History of MI, stroke, any surgical or percutaneous revascularization procedure, use of any antihypertensive/lipid-lowering drugs, coronary/carotid/peripheral artery disease, hypertension
* Type 2 diabetes
* BMI ≥25.0kg/m2
* Age ≥18 years
* Male or female sex


* History of MI, stroke, any surgical or percutaneous revascularization procedure, use of any antihypertensive/lipid-lowering drugs, coronary/carotid/peripheral artery disease, hypertension
* Type 2 diabetes
* BMI ≥25.0kg/m2
* Age ≥18 years
* Male or female sex


* History of MI, stroke, any surgical or percutaneous revascularization procedure, use of any antihypertensive/lipid-lowering drugs, coronary/carotid/peripheral artery disease, hypertension
* Type 2 diabetes
* BMI ≥25.0kg/m2
* Age ≥18 years
* Male or female sex

Exclusion Criteria

* Medullary thyroid carcinoma, MEN syndrome type 2
* Malignancy
* Type 1 diabetes or secondary diabetes
* Chronic kidney disease or dialysis
* Uncontrolled diabetic retinopathy or maculopathy
* Pregnancy
* Prior use of pramlintide or any GLP-1-RA

ELIGIBILITY FOR SEMAGLUTIDE VS SITAGLIPTIN


* Medullary thyroid carcinoma, MEN syndrome type 2
* Malignancy
* Type 1 diabetes or secondary diabetes
* Chronic kidney disease or dialysis
* Uncontrolled diabetic retinopathy or maculopathy
* Pregnancy
* Prior use of pramlintide or any GLP-1-RA or DPP4i

ELIGIBILITY FOR TIRZEPATIDE VS SEMAGLUTIDE


* Medullary thyroid carcinoma, MEN syndrome type 2
* Malignancy
* Type 1 diabetes or secondary diabetes
* Chronic kidney disease or dialysis
* Uncontrolled diabetic retinopathy or maculopathy
* Pregnancy
* Prior use of pramlintide or any GLP-1-RA
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Shirley Vichy Wang

Associate Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shirley Wang, PhD, ScM

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Nils Krüger, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Study Protocol and Statistical Analysis Plan: Amendment to Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2018P002966-DUP-TIRZSEMA-CVOT

Identifier Type: -

Identifier Source: org_study_id

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