Diabetes Mellitus, Type 2DUP-TIRZSEMANCT06914141
Comparative Effectiveness of Tirzepatide Versus Semaglutide in Individuals With Heart Failure With Preserved Ejection Fraction
An observational study of Diabetes Mellitus, Type 2 and HFpEF - Heart Failure With Preserved Ejection Fraction, 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
- Diabetes Mellitus, Type 2, HFpEF - Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Tirzepatide and Semaglutide
- How many people
- 28,118 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2025to 1 Jun 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: The study population includes individuals aged 40 years or older with heart failure with preserved ejection fraction.
Who may be able to join
- Heart failure
- BMI > 27.0 kg/m2
- History of type 2 diabetes mellitus
- LVEF ≥ 45%
- ≥ 18 years old, male or female sex
Who cannot join
- Prior treatment with any GLP-1-RA
- History of type 1 diabetes mellitus
- End-stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
- History of bariatric surgery
- History of nursing home admission
- Pregnant female or breastfeeding
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- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy
- Treatment with continuous subcutaneous insulin infusion
- Multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
- Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) for less than 5 years
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 semaglutide after emulating the pivotal RCTs of each drug used to support regulatory approval in heart failure with preserved ejection fraction (SUMMIT and STEP-HFpEF DM trials).This comparative effectiveness target trial described below draws from eligibility criteria from the SUMMIT and STEP-HFpEF DM trials. 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 2 national United States claims databases, where we compare the effect of tirzepatide vs semaglutide on the composite end point of all-cause mortality or heart failure hospitalization. Clinical guidelines during the study period recommended both agents for the same indications of glucose lowering and weight reduction. Indication for heart failure with preserved ejection fraction has not been granted for both drugs during the study period.
- Being tested
- Tirzepatide, Semaglutide
- Medical subject headings
- Diabetes Mellitus, Type 2
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.
SemaglutideDrug
New use of semaglutide dispensing claim is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| Tirzepatide | New use of tirzepatide dispensing claim is used as the exposure. Receives: Drug: Tirzepatide | |
| Semaglutide | New use of semaglutide dispensing claim is used as the reference. 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 or heart failure hospitalization
To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or heart failure hospitalization in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Secondary outcomes (8)
Composite of all-cause mortality or all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting).
To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or worsening heart failure events in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).
To evaluate the comparative effect of tirzepatide vs semaglutide on worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting) in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Intravenous diuretic therapy in an urgent care setting
To evaluate the comparative effect of tirzepatide vs semaglutide on intravenous diuretic therapy in an urgent care setting in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Hospitalization for heart failure
To evaluate the comparative effect of tirzepatide vs semaglutide on hospitalization for heart failure in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
All-cause mortality
To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Urinary tract infection
To evaluate the comparative effect of tirzepatide vs semaglutide on urinary tract infection in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Serious bacterial infection
To evaluate the comparative effect of tirzepatide vs semaglutide on serious bacterial infection in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Gastrointestinal adverse events
To evaluate the comparative effect of tirzepatide vs semaglutide on gastrointestinal adverse events in patients with heart failure with preserved ejection fraction.
Measured: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2025
- Study start14 Jan 2025
- Primary completion1 Jun 2025
- Study completion1 Jun 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 Diabetes Mellitus, Type 2Studies 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
- 28,118 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
- NCT06914141
- Sponsor's protocol ID
- 2018P002966-DUP-TIRZSEMA
- Acronym
- DUP-TIRZSEMA
- Status last verified
- May 2025
- First submitted
- 31 Mar 2025
- Last updated
- 30 Jan 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kruger N, Schneeweiss S, Fuse K, Matseyko S, Sreedhara SK, Hahn G, Schunkert H, Wang SV. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092.
PubMed 40886075
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Tirzepatide Versus Semaglutide in Individuals With Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT06914141
- Acronym / sponsor ID
- DUP-TIRZSEMA / 2018P002966-DUP-TIRZSEMA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28,118 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 14 Jan 2025 (actual)
- Primary completion
- 1 Jun 2025 (actual)
- Study completion
- 1 Jun 2025 (actual)
- First posted
- 6 Apr 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 semaglutide after emulating the pivotal RCTs of each drug used to support regulatory approval in heart failure with preserved ejection fraction (SUMMIT and STEP-HFpEF DM trials).This comparative effectiveness target trial described below draws from eligibility criteria from the SUMMIT and STEP-HFpEF DM trials. 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 2 national United States claims databases, where we compare the effect of tirzepatide vs semaglutide on the composite end point of all-cause mortality or heart failure hospitalization. Clinical guidelines during the study period recommended both agents for the same indications of glucose lowering and weight reduction. Indication for heart failure with preserved ejection fraction has not been granted for both drugs during the study period.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tirzepatide | – | Drug: TirzepatideNew use of tirzepatide dispensing claim is used as the exposure. |
| Semaglutide | – | Drug: SemaglutideNew use of semaglutide dispensing claim is used as the reference. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes individuals aged 40 years or older with heart failure with preserved ejection fraction.
Key inclusion criteria (5 listed)
- Heart failure
- BMI > 27.0 kg/m2
- History of type 2 diabetes mellitus
- LVEF ≥ 45%
- ≥ 18 years old, male or female sex
Key exclusion criteria (10 listed)
- Prior treatment with any GLP-1-RA
- History of type 1 diabetes mellitus
- End-stage renal disease or chronic or intermittent haemodialysis or peritoneal dialysis
- History of bariatric surgery
- History of nursing home admission
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 |
|---|---|---|
| TirzepatideNew use of tirzepatide dispensing claim is used as the exposure. | Drug | Tirzepatide |
| SemaglutideNew use of semaglutide dispensing claim is used as the reference. | Drug | Semaglutide |
Primary outcome
Composite of all-cause mortality or heart failure hospitalization
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
To evaluate the comparative effect of tirzepatide vs semaglutide on all-cause mortality or heart failure hospitalization in patients with heart failure with preserved ejection fraction.
8 secondary outcomes
Composite of all-cause mortality or all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting).
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting).
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Intravenous diuretic therapy in an urgent care setting
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Hospitalization for heart failure
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
All-cause mortality
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Urinary tract infection
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Serious bacterial infection
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Gastrointestinal adverse events
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
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 Jan 2026.
- Derived from this study: PubMed 40886075Kruger N, Schneeweiss S, Fuse K, Matseyko S, Sreedhara SK, Hahn G, Schunkert H, Wang SV. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092.
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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 Diabetes Mellitus, Type 2 and HFpEF - Heart Failure With Preserved Ejection Fraction, 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 10 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 Jan 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 or heart failure hospitalization (time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)). 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 NCT06914141, 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 Jan 2026.