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Type 2 DiabetesTIRZSEMA-CVOTNCT07096063

Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk

An observational study of Type 2 Diabetes and Overweight, run by Brigham and Women's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tirzepatide, Dulaglutide and Semaglutide
How many people
887,132 participants
Where
1 siteUnited States
Study dates
1 Oct 2024to 15 Jul 2025
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Individuals typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes mellitus and overweight.

Who may be able to join

  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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
Show all 23Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Brigham and Women's Hospital

    Boston, Massachusetts, 02120

Other trials in United States

About this study

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.

Read the 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.

Being tested
Tirzepatide, Dulaglutide, Semaglutide, Sitagliptin
Medical subject headings
Diabetes Mellitus, Type 2, Overweight

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TirzepatideDrug

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

  • DulaglutideDrug

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

  • SemaglutideDrug

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

  • SitagliptinDrug

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

Study groups in NCT07096063
Study groupRoleWhat they receive
Cohort 1Tirzepatide vs dulaglutide
Receives: Drug: Tirzepatide; Drug: Dulaglutide
Cohort 2Semaglutide vs sitagliptin
Receives: Drug: Semaglutide; Drug: Sitagliptin
Cohort 3Tirzepatide vs semaglutide
Receives: Drug: Tirzepatide; Drug: Semaglutide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of all-cause mortality, myocardial infarction or stroke (Tirzepatide vs. dulaglutide)

    To evaluate the comparative effect of tirzepatide vs dulaglutide on the composite of all-cause mortality, myocardial infarction, or death in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  2. Composite of all-cause mortality, myocardial infarction or stroke (Injectable semaglutide vs sitagliptin)

    To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the composite of all-cause mortality, myocardial infarction, or death in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  3. Composite of all-cause mortality, myocardial infarction or stroke (Tirzepatide vs injectable semaglutide)

    To evaluate the comparative effect of tirzepatide vs semaglutide on the composite of all-cause mortality, myocardial infarction, or death in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

Secondary outcomes (15)
  1. Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke (Tirzepatide vs dulaglutide)

    To evaluate the comparative effect of tirzepatide vs dulaglutide on the individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  2. Composite of all-cause mortality, hospitalization for heart failure, or urgent heart failure visits requiring intravenous diuretics (Tirzepatide vs dulaglutide)

    To evaluate the comparative effect of tirzepatide vs dulaglutide on all-cause mortality, hospitalization for heart failure, or urgent heart failure visits in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  3. Urinary tract infections (Tirzepatide vs dulaglutide)

    To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of urinary tract infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  4. Serious bacterial infections (Tirzepatide vs dulaglutide)

    To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of serious bacterial infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  5. Gastrointestinal adverse events (Tirzepatide vs dulaglutide)

    To evaluate the comparative effect of tirzepatide vs dulaglutide on the safety outcome of gastrointestinal adverse events in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  6. Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke (Injectable semaglutide vs sitagliptin)

    To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  7. Composite of all-cause mortality, hospitalization for heart failure, or urgent heart failure visits requiring intravenous diuretics (Injectable semaglutide vs sitagliptin)

    To evaluate the comparative effect of injectable semaglutide vs sitagliptin on all-cause mortality, hospitalization for heart failure, or urgent heart failure visits in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  8. Urinary tract infections (Injectable semaglutide vs sitagliptin)

    To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the safety outcome of urinary tract infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  9. Serious bacterial infections (Injectable semaglutide vs sitagliptin)

    To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the safety outcome of serious bacterial infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  10. Gastrointestinal adverse events (Injectable semaglutide vs sitagliptin)

    To evaluate the comparative effect of injectable semaglutide vs sitagliptin on the safety outcome of gastrointestinal adverse events in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  11. Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke (Tirzepatide vs injectable semaglutide)

    To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  12. Composite of all-cause mortality, hospitalization for heart failure, or urgent heart failure visits requiring intravenous diuretics (Tirzepatide vs injectable semaglutide)

    To evaluate the comparative effect of tirzepatide vs injectable semaglutide on all-cause mortality, hospitalization for heart failure, or urgent heart failure visits in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  13. Urinary tract infections (Tirzepatide vs injectable semaglutide)

    To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the safety outcome of urinary tract infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  14. Serious bacterial infections (Tirzepatide vs injectable semaglutide)

    To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the safety outcome of serious bacterial infections in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

  15. Gastrointestinal adverse events (Tirzepatide vs injectable semaglutide)

    To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the safety outcome of gastrointestinal adverse events in patients typically treated in clinical practice who are at cardiovascular risk with type 2 diabetes and overweight.

    Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2025
  2. Study start1 Oct 2024
  3. Primary completion15 Jul 2025
  4. Study completion15 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Retrospective
Enrolment
887,132 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07096063
Sponsor's protocol ID
2018P002966-DUP-TIRZSEMA-CVOT
Acronym
TIRZSEMA-CVOT
Status last verified
Aug 2025
First submitted
23 Jul 2025
Last updated
15 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Kruger N, Schneeweiss S, Desai RJ, Sreedhara SK, Kehoe AR, Fuse K, Hahn G, Schunkert H, Wang SV. Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. Nat Med. 2026 Jan;32(1):342-352. doi: 10.1038/s41591-025-04102-x. Epub 2025 Nov 9.

    PubMed 41207920

Questions about this trial

What is this clinical trial studying?

An observational study of Type 2 Diabetes and Overweight, run by Brigham and Women's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of all-cause mortality, myocardial infarction or stroke (Tirzepatide vs. dulaglutide) (time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07096063, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2025.

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