ObesityNCT07619508
Tirzepatide vs Semaglutide in Individuals at Cardiovascular Risk But Without Diabetes.
An observational study of Obesity and Overweight, 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 18 years and older
- Conditions the study is for
- Obesity, Overweight
- What is being tested?
- Tirzepatide and Semaglutide
- Type of treatment
- Injection or infusion
- How many people
- 100,000 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2026to 1 Jun 2026
- 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 aged 18 years or older at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice
Who may be able to join
- Men or women aged 18 years or older
- History of myocardial infarction, stroke, any surgical or percutaneous revascularization procedure
- Use of antihypertensive or lipid-lowering drugs
- Coronary, carotid, or peripheral artery disease
- BMI greater than or equal to 25.0 mg/m2
Who cannot join
- Medullary thyroid carcinoma
- MEN syndrome type 2
- Malignancy
- Type 1 diabetes
- Type 2 diabetes
- Secondary diabetes
Show all 11Show fewer
- End-stage renal disease or dialysis
- Pregnancy
- History of bariatric surgery
- Prior use of pramlintide or any GLP-1-RA, except tirzepatide or semaglutide
- Cardiovascular event or intervention in the last 7 days
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02120
About this study
Official title: Comparative Effectiveness of Tirzepatide and Semaglutide in Patients at Cardiovascular Risk With Overweight or Obesity But Without Diabetes
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 semaglutide on cardiovascular outcomes among patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
The SELECT trial (NCT03574597) demonstrated that semaglutide reduces major adverse cardiovascular events in individuals with established cardiovascular disease and overweight or obesity but without diabetes. Whether tirzepatide provides similar cardiovascular benefit in patients without diabetes is being evaluated in the ongoing placebo-controlled SURMOUNT-MMO trial (NCT05556512), with results expected in late 2027. Although SURMOUNT-MMO will assess the cardiovascular efficacy of tirzepatide in individuals without diabetes, evidence to inform treatment choices among available incretin-based therapies in clinical practice is urgently needed. Therefore, this study examines the comparative effectiveness of tirzepatide vs semaglutide among patients at cardiovascular risk with overweight or obesity but without diabetes in clinical practice.
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 database study will be a new-user active-comparative study, conducted using 3 national United States claims databases, where we compare the effect of 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
- Obesity, Overweight
- Being tested
- Tirzepatide, Semaglutide
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Initiation of tirzepatide described in electronic health records is used as the exposure.
SemaglutideDrug
Initiation of injectable semaglutide described in electronic health records is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide | Exposure group Receives: Drug: Tirzepatide | |
| Injectable semaglutide | Reference group Receives: Drug: Semaglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of all-cause mortality, myocardial infarction, or stroke.
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the composite of death, myocardial infarction, or stroke in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
Measured: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Secondary outcomes (5)
Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the individual components of the primary endpoint, i.e., death, myocardial infarction, or stroke in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
Measured: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
Measured: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Hospitalization for heart failure
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the occurrence of heart failure hospitalizations in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
Measured: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Hospitalization for unstable angina
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the occurrence of hospitalizations for unstable angina in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
Measured: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Coronary revascularization
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the occurrence of coronary revascularization in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
Measured: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2026
- Study start10 Feb 2026
- Primary completion1 Jun 2026
- Study completion1 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies 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
- 100,000 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
- NCT07619508
- Sponsor's protocol ID
- 2018P002966-TIRZSEMA-MMO
- Status last verified
- May 2026
- First submitted
- 23 May 2026
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Tirzepatide and Semaglutide in Patients at Cardiovascular Risk With Overweight or Obesity But Without Diabetes
- ClinicalTrials.gov ID
- NCT07619508
- Acronym / sponsor ID
- 2018P002966-TIRZSEMA-MMO
- Conditions
- Obesity, Overweight
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100,000 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 10 Feb 2026 (actual)
- Primary completion
- 1 Jun 2026 (actual)
- Study completion
- 1 Jun 2026 (actual)
- First posted
- 2 Jun 2026 (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 semaglutide on cardiovascular outcomes among patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
The SELECT trial (NCT03574597) demonstrated that semaglutide reduces major adverse cardiovascular events in individuals with established cardiovascular disease and overweight or obesity but without diabetes. Whether tirzepatide provides similar cardiovascular benefit in patients without diabetes is being evaluated in the ongoing placebo-controlled SURMOUNT-MMO trial (NCT05556512), with results expected in late 2027. Although SURMOUNT-MMO will assess the cardiovascular efficacy of tirzepatide in individuals without diabetes, evidence to inform treatment choices among available incretin-based therapies in clinical practice is urgently needed. Therefore, this study examines the comparative effectiveness of tirzepatide vs semaglutide among patients at cardiovascular risk with overweight or obesity but without diabetes in clinical practice.
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 database study will be a new-user active-comparative study, conducted using 3 national United States claims databases, where we compare the effect of 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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide | – | Drug: TirzepatideExposure group |
| Injectable semaglutide | – | Drug: SemaglutideReference group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals aged 18 years or older at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice
Key inclusion criteria (5 listed)
- Men or women aged 18 years or older
- History of myocardial infarction, stroke, any surgical or percutaneous revascularization procedure
- Use of antihypertensive or lipid-lowering drugs
- Coronary, carotid, or peripheral artery disease
- BMI greater than or equal to 25.0 mg/m2
Key exclusion criteria (11 listed)
- Medullary thyroid carcinoma
- MEN syndrome type 2
- Malignancy
- Type 1 diabetes
- Type 2 diabetes
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 |
|---|---|---|
| TirzepatideInitiation of tirzepatide described in electronic health records is used as the exposure. | Drug | Tirzepatide |
| SemaglutideInitiation of injectable semaglutide described in electronic health records is used as the reference. | Drug | Injectable semaglutide |
Primary outcome
Composite of all-cause mortality, myocardial infarction, or stroke.
Time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
To evaluate the comparative effect of tirzepatide vs injectable semaglutide on the composite of death, myocardial infarction, or stroke in patients at cardiovascular risk with overweight or obesity but without diabetes treated in clinical practice.
5 secondary outcomes
Individual components of the primary endpoint, i.e., all-cause mortality, myocardial infarction, or stroke
Time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Composite of myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure
Time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Hospitalization for heart failure
Time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Hospitalization for unstable angina
Time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
Coronary revascularization
Time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA
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 9 Jul 2026.
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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 Obesity 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 5 inclusion and 11 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 9 Jul 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?
Composite of all-cause mortality, myocardial infarction, or stroke. (time frame: 1 day after prescription fill of exposure or comparator until outcome, end of data, end of study period, death, discontinuation (45 day grace, risk-window), nursing home admission, augmentation/additional exposure or switch to comparator or other GLP1-RA). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2026.