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TIRZSEMA-CVOT

Completed

Comparative Effectiveness of Tirzepatide and Semaglutide in Individuals at Cardiovascular Risk

Lead sponsor

Brigham and Women's Hospital

Assets

Dulaglutide / Semaglutide / Tirzepatide

Listed sites

Recruiting sites

—

Enrollment

887,132

actual

Study population

Cardiovascular disease, Obesity / overweight, Type 2 diabetes

Key I/E criterion

•BMI ≥25

Primary endpoint

•Expanded / custom MACE composite (All-cause death, Myocardial infarction (any), Stroke (any))

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07096063

Org study ID2018P002966-DUP-TIRZSEMA-CVOT

Timeline

Milestones

Study start2024-10-01actual

Primary completion2025-07-15actual

Study completion2025-07-15actual

Study first posted2025-07-31actual

Last update posted2025-10-15actual

Assets

Investigational agents

Dulaglutide Semaglutide Tirzepatide

Study populations

Who this study enrolls

Cardiovascular diseaseObesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Sampling methodNon probability sample

Study population text

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

Inclusion criteria

ELIGIBILITY FOR TIRZEPATIDE VS DULAGLUTIDE

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

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

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

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 or DPP4i

ELIGIBILITY FOR TIRZEPATIDE VS SEMAGLUTIDE

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

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

Endpoints (24)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Cardiovascular outcomes

Other clinical outcomes

Heart failure

Cardiovascular outcomes

6 endpoints

Primary/protocol endpoint

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

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Myocardial infarction (any), Stroke (any)

Primary/protocol endpoint

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

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

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Myocardial infarction (any), Stroke (any)

Primary/protocol endpoint

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

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

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Myocardial infarction (any), Stroke (any)

Secondary/protocol endpoint

Individual components of the primary endpoint, i.e., 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

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Myocardial infarction (any), Stroke (any)

Secondary/protocol endpoint

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

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

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Myocardial infarction (any), Stroke (any)

Secondary/protocol endpoint

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

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

time to event, event

Heart failure

3 endpoints

Secondary/protocol endpoint

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

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

Heart-failure composite

time to event, event

componentsAll-cause death, Heart-failure hospitalization, Urgent heart-failure visit

Secondary/protocol endpoint

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

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

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Heart-failure hospitalization, Urgent heart-failure visit

Secondary/protocol endpoint

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

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

Heart-failure composite

time to event, event

componentsAll-cause death, Heart-failure hospitalization, Urgent heart-failure visit

Safety / tolerability / PK

11 endpoints

Secondary/protocol endpoint

Urinary tract infections (Tirzepatide vs dulaglutide)

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

time to event, event

Secondary/protocol endpoint

Serious bacterial infections (Tirzepatide vs dulaglutide)

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

time to event, event

Secondary/protocol endpoint

Gastrointestinal adverse events (Tirzepatide vs dulaglutide)

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

time to event, event

Secondary/protocol endpoint

Urinary tract infections (Injectable semaglutide vs sitagliptin)

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

time to event, event

Secondary/protocol endpoint

Serious bacterial infections (Injectable semaglutide vs sitagliptin)

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

time to event, event

Secondary/protocol endpoint

Gastrointestinal adverse events (Injectable semaglutide vs sitagliptin)

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

time to event, event

Secondary/protocol endpoint

Urinary tract infections (Tirzepatide vs injectable semaglutide)

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

time to event, event

Secondary/protocol endpoint

Serious bacterial infections (Tirzepatide vs injectable semaglutide)

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

time to event, event

Secondary/protocol endpoint

Gastrointestinal adverse events (Tirzepatide vs injectable semaglutide)

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

time to event, event

Other/protocol endpoint

Hernia (Tirzepatide vs dulaglutide)

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

time to event, event

Other/protocol endpoint

Hernia (Tirzepatide vs injectable semaglutide)

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

time to event, event

Other clinical outcomes

4 endpoints

Other/protocol endpoint

Lumbar radiculopathy (Tirzepatide vs dulaglutide)

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

time to event, event

Other/protocol endpoint

Hernia (Injectable semaglutide vs sitagliptin)

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

time to event, event

Other/protocol endpoint

Lumbar radiculopathy (Injectable semaglutide vs sitagliptin)

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

time to event, event

Other/protocol endpoint

Lumbar radiculopathy (Tirzepatide vs injectable semaglutide)

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

time to event, event

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice.
Nature medicine2026 Jan (month)PMID41207920doi:10.1038/s41591-025-04102-xvia clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.