Type2 Diabetes MellitusNCT07203677
Comparative Effectiveness of Tirzepatide Versus Sitagliptin in Individuals at Cardiovascular Risk (TIRZSITA-CVOT)
An observational study of Type2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease, run by Brigham and Women's Hospital at 1 site in United States.
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 40 years and older
- Conditions the study is for
- Type2 Diabetes Mellitus, Atherosclerotic Cardiovascular Disease
- What is being tested?
- Initiation of tirzepatide and Initiation of sitagliptin
- How many people
- 49,065 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Sep 2025to 15 Oct 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Individuals aged 40 years or older with T2DM and and atherosclerotic cardiovascular disease.
Who may be able to join
- History of MI or stroke, surgical or percutaneous coronary/carotid peripheral artery revascularization, amputation, diagnosis of coronary/carotid/peripheral artery disease
- BMI ≥25.0kg/m2
- Type 2 diabetes
- Age ≥40 years
- Male or female sex
Who cannot join
- Medullary thyroid carcinoma, MEN syndrome type 2, malignancy
- Treatment for diabetic retinopathy/macular edema, heart failure NYHA IV, gastric emptying abnormality/bariatric surgery, end-stage renal disease or dialysis, pregnancy
- Prior use of pramlintide or any GLP-1-RA except tirzepatide,
- Pancreatitis, liver disease
- Cardiovascular event or intervention, hospitalization for heart failure
- Concurrent use of both drugs i.e. tirzepatide and sitagliptin
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
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 tirzepatide vs sitagliptin as a placebo proxy, after the pivotal RCT SURPASS-CVOT (NCT04255433) and its emulation (NCT07088718) demonstrated non-inferiority, leaving both regulators and clinical guideline committees uncertain whether to approve and recommend tirzepatide for a cardiovascular indication. This comparative effectiveness target trial described below draws from eligibility criteria from the SURPASS-CVOT trial and its emulation. Although many features of the target trial 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 purpose of this protocol is to specify the target trial assessing the comparative effectiveness of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1-RA) tirzepatide vs the dipeptidyl peptidase-4 inhibitors (DPP4i) sitagliptin on atherosclerotic cardiovascular end points in patients with type 2 diabetes and atherosclerotic cardiovascular disease.
The database study will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs sitagliptin in preventing atherosclerotic cardiovascular events. Clinical guidelines during the study period recommended both agents under investigation as second-line options for glucose lowering and were similarly costly.
- Being tested
- Initiation of tirzepatide, Initiation of sitagliptin
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Initiation of tirzepatideDrug
New use of tirzepatide dispensing claim is used as the exposure.
Initiation of sitagliptinDrug
New use of sitagliptin dispensing claim is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| Initiation of tirzepatide | Exposure group Receives: Drug: Initiation of tirzepatide | |
| Initiation of sitagliptin | Reference group Receives: Drug: Initiation of sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major adverse cardiovascular events
To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction, stroke, or all-cause mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Secondary outcomes (10)
Composite of myocardial infarction or stroke
To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction or stroke in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Myocardial infarction
To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing myocardial infarction in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Stroke
To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing stroke in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
All-cause mortality
To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing all-cause mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Infection-related mortality
To evaluate the comparative effect of tirzepatide vs sitagliptin at preventing infection-related mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Composite of myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.
To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Serious bacterial infections
To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of serious bacterial infections in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Urinary tract infections
To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of urinary tract infections in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Gastrointestinal adverse events
To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of gastrointestinal adverse events in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
Measured: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Infections across care settings
To evaluate the comparative effect of tirzepatide vs sitagliptin on the safety outcome of infections across care settings in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
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.
- First posted2 Oct 2025
- Study start19 Sep 2025
- Primary completion15 Oct 2025
- Study completion15 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 49,065 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shirley Vichy Wang, Brigham and Women's Hospital
- Investigators
- Shirley Wang, PhD, ScM, Principal investigator, Brigham and Women's HospitalNils Krüger, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07203677
- Sponsor's protocol ID
- 2018P002966-DUP-TIRZSITA
- Status last verified
- Sep 2025
- First submitted
- 25 Sep 2025
- Last updated
- 30 Apr 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kruger N, Schneeweiss S, Wang SV. Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study. BMJ. 2026 Aug 5;394:e100011. doi: 10.1136/bmj-2026-100011.
PubMed 42556854
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Tirzepatide Versus Sitagliptin in Individuals at Cardiovascular Risk (TIRZSITA-CVOT)
- ClinicalTrials.gov ID
- NCT07203677
- Acronym / sponsor ID
- 2018P002966-DUP-TIRZSITA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 49,065 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 19 Sep 2025 (actual)
- Primary completion
- 15 Oct 2025 (actual)
- Study completion
- 15 Oct 2025 (actual)
- First posted
- 2 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 tirzepatide vs sitagliptin as a placebo proxy, after the pivotal RCT SURPASS-CVOT (NCT04255433) and its emulation (NCT07088718) demonstrated non-inferiority, leaving both regulators and clinical guideline committees uncertain whether to approve and recommend tirzepatide for a cardiovascular indication. This comparative effectiveness target trial described below draws from eligibility criteria from the SURPASS-CVOT trial and its emulation. Although many features of the target trial 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 purpose of this protocol is to specify the target trial assessing the comparative effectiveness of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1-RA) tirzepatide vs the dipeptidyl peptidase-4 inhibitors (DPP4i) sitagliptin on atherosclerotic cardiovascular end points in patients with type 2 diabetes and atherosclerotic cardiovascular disease.
The database study will be a new-user active-comparative study, conducted using 2 national United States claims databases, where we compare the effect of tirzepatide vs sitagliptin in preventing atherosclerotic cardiovascular events. Clinical guidelines during the study period recommended both agents under investigation as second-line options for glucose lowering and were similarly costly.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Initiation of tirzepatide | – | Drug: Initiation of tirzepatideExposure group |
| Initiation of sitagliptin | – | Drug: Initiation of sitagliptinReference group |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals aged 40 years or older with T2DM and and atherosclerotic cardiovascular disease.
Key inclusion criteria (5 listed)
- History of MI or stroke, surgical or percutaneous coronary/carotid peripheral artery revascularization, amputation, diagnosis of coronary/carotid/peripheral artery disease
- BMI ≥25.0kg/m2
- Type 2 diabetes
- Age ≥40 years
- Male or female sex
Key exclusion criteria (6 listed)
- Medullary thyroid carcinoma, MEN syndrome type 2, malignancy
- Treatment for diabetic retinopathy/macular edema, heart failure NYHA IV, gastric emptying abnormality/bariatric surgery, end-stage renal disease or dialysis, pregnancy
- Prior use of pramlintide or any GLP-1-RA except tirzepatide,
- Pancreatitis, liver disease
- Cardiovascular event or intervention, hospitalization for heart failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Initiation of tirzepatideNew use of tirzepatide dispensing claim is used as the exposure. | Drug | Initiation of tirzepatide |
| Initiation of sitagliptinNew use of sitagliptin dispensing claim is used as the reference. | Drug | Initiation of sitagliptin |
Primary outcome
Major adverse cardiovascular events
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
To evaluate the comparative effect of tirzepatide vs sitagliptin on the composite of myocardial infarction, stroke, or all-cause mortality in patients with type 2 diabetes and atherosclerotic cardiovascular disease when following the inclusion and exclusion criteria of the SURPASS-CVOT trial.
10 secondary outcomes
Composite of myocardial infarction or stroke
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Myocardial infarction
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Stroke
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
All-cause mortality
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Infection-related mortality
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Composite of myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Serious bacterial infections
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Urinary tract infections
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Gastrointestinal adverse events
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Infections across care settings
Time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2026.
- Derived from this study: PubMed 42556854Kruger N, Schneeweiss S, Wang SV. Tirzepatide and the risk of atherosclerotic cardiovascular events: population based cohort study. BMJ. 2026 Aug 5;394:e100011. doi: 10.1136/bmj-2026-100011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shirley Wang, PhD, ScM principal investigator
Brigham and Women's Hospital
Nils Krüger, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease, 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 5 inclusion and 6 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 30 Apr 2026. 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?
Major adverse cardiovascular events (time frame: 1 day after cohort entry date until the first of outcome or censoring, up to 365 days). 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 NCT07203677, 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 30 Apr 2026.