Type 2 DiabetesNCT07417631
Emulation of the REWIND Cardiovascular Outcomes Trial in Healthcare Claims Data.
An observational study of Type 2 Diabetes, 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 50 years and older
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Dulaglutide and Sitagliptin
- How many people
- 300,000 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Feb 2026to 15 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Two populations: (1) Individuals with T2DM, who are either aged 50 years or above with an established cardiovascular disease, aged 55 years or above with a subclinical cardiovascular disease, or aged 60 years or above with at least two cardiovascular risk factors; and (2) individuals typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with T2DM.
Who may be able to join
- MI, Stroke, Revascularization procedure, Diagnosis of coronary/carotid/peripheral artery disease, diagnosis of hypertensive heart disease
- BMI >= 23.0kg/m2
- Type 2 Diabetes Mellitus
- Chronic Kidney Disease (CKD) Stage 3/4
- Albuminuria
- Tobacco use
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- Hypercholesterolemia/-lipidemia
- Stable dose of glucose-lowering drugs, use lipid-lowering drugs, use of blood pressure medication
- History of MI, stroke, any surgical or percutaneous revascularization procedure, use of antihypertensive/ lipid-lowering drugs, coronary / carotid / peripheral artery disease
- BMI >= 25.0kg/m2
- Type 2 Diabetes
Who cannot join
- MEN syndrome or medullary thyroid carcinoma, organ transplant, malignancy
- Severe hypoglycemic episode
- CKD stage 5 or dialysis
- Gastric emptying abnormality or bariatric surgery
- Pregnancy
- Craniocervical Instability (CCI)
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- Pancreatitis
- Liver disease
- Weight loss drug
- Uncontrolled diabetes
- Acute coronary/cerebrovascular event
- Concurrent use of both study drugs
- EXPANDED POPULATION:
- Medullary thyroid carcinoma,
- MEN syndrome type 2
- Malignancy
- Type 1 diabetes or secondary diabetes
- End-stage renal disease or dialysis
- Uncontrolled diabetic retinopathy or maculopathy
- Pregnancy
- Bariatric surgery
- Prior use of pramlintide or any GLP-1-RA except dulaglutide, or any DPP4i except 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 emulate, as closely as possible in healthcare insurance claims data, the REWIND trial described below. Although many features of the 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 trial. In addition to closely emulating the trial population, this study also evaluates outcomes in an expanded cohort following the eligibility criteria outlined in a set of completed emulation studies (NCT06659744, NCT07088718, NCT07096063) to enhance generalizability to patients typically encountered in clinical practice. Randomization cannot be emulated in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
The REWIND (NCT01394952) trial is a superiority trial that evaluated the effect of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1-RA), vs placebo on time to first occurrence of any major adverse cardiovascular event (MACE), defined as cardiovascular death, myocardial infarction, or stroke among patients with type 2 diabetes mellitus (T2DM) with and without previous cardiovascular disease (CVD).
The database study designed to emulate the REWIND trial will be a new-user active comparative study, where we compare the effect of dulaglutide vs sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4i), on MACE among patients with T2DM with and without previous CVD. While the REWIND trial compared dulaglutide vs placebo, we chose to use sitagliptin as an active-comparator proxy for placebo. Sitagliptin was specifically chosen because a major randomized controlled trial on cardiovascular outcomes demonstrated that the drug does not affect the cardiovascular outcomes under investigation. Furthermore, clinical guidelines during the study period recommended both drug classes under investigation as second- or third-line options for glucose lowering and were similarly costly.
- Conditions
- Type 2 Diabetes
- Being tested
- Dulaglutide, Sitagliptin
- 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.
DulaglutideDrug
Initiation of dulaglutide dispensing claim is used as the exposure.
SitagliptinDrug
Initiation of sitagliptin dispensing claim is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| Initiation of dulaglutide | Exposure group Receives: Drug: Dulaglutide | |
| Initiation of sitagliptin | Reference group Receives: Drug: Sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to first occurrence of myocardial infarction, stroke, or all-cause mortality
The primary outcome is the time from cohort entry to the first occurrence of any component of the composite endpoint: myocardial infarction, stroke, or all-cause mortality in patients with T2DM with and without previous CVD, comparing dulaglutide versus sitagliptin, when following the eligibility criteria of the REWIND trial.
Measured: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
Time to first occurrence of myocardial infarction, stroke, or all-cause mortality
The outcome is the time from cohort entry to the first occurrence of any component of the composite endpoint: myocardial infarction, stroke, or all-cause mortality in patients with T2DM with and without previous CVD, comparing dulaglutide versus sitagliptin, when expanding the eligibility criteria of the REWIND trial.
Measured: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
Secondary outcomes (3)
Time to first occurrence of myocardial infarction, stroke, or all-cause mortality, assessed as individual components
The outcomes are the times from cohort entry to the first occurrence of each individual component of the primary composite endpoint: myocardial infarction, stroke, and all-cause mortality, comparing dulaglutide versus sitagliptin in a patient population defined by expanded REWIND eligibility criteria.
Measured: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
Time to first occurrence of a heart failure event
The outcome is the time from cohort entry to the first heart failure event, defined as exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting, comparing dulaglutide versus sitagliptin in a broader patient population defined by expanded REWIND eligibility criteria.
Measured: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
Time to first occurrence of unstable angina
The outcome is the time from cohort entry to the first occurrence of unstable angina, comparing dulaglutide versus sitagliptin in a broader patient population defined by expanded REWIND eligibility criteria.
Measured: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2026
- Study start3 Feb 2026
- Primary completion15 Jun 2026
- Study completion15 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies 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
- 300,000 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
- NCT07417631
- Sponsor's protocol ID
- 2018P002966-REWIND
- Status last verified
- Feb 2026
- First submitted
- 11 Feb 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emulation of the REWIND Cardiovascular Outcomes Trial in Healthcare Claims Data.
- ClinicalTrials.gov ID
- NCT07417631
- Acronym / sponsor ID
- 2018P002966-REWIND
- Conditions
- Type 2 Diabetes
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 300,000 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 3 Feb 2026 (actual)
- Primary completion
- 15 Jun 2026 (actual)
- Study completion
- 15 Jun 2026 (actual)
- First posted
- 18 Feb 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 emulate, as closely as possible in healthcare insurance claims data, the REWIND trial described below. Although many features of the 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 trial. In addition to closely emulating the trial population, this study also evaluates outcomes in an expanded cohort following the eligibility criteria outlined in a set of completed emulation studies (NCT06659744, NCT07088718, NCT07096063) to enhance generalizability to patients typically encountered in clinical practice. Randomization cannot be emulated in healthcare claims data but was proxied through a statistical balancing of measured covariates according to standard practice. Investigators assume that the RCT provides the reference standard treatment effect estimate and that failure to replicate RCT findings is indicative of the inadequacy of the healthcare claims data for emulation for a range of possible reasons and does not provide information on the validity of the original RCT finding.
The REWIND (NCT01394952) trial is a superiority trial that evaluated the effect of dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1-RA), vs placebo on time to first occurrence of any major adverse cardiovascular event (MACE), defined as cardiovascular death, myocardial infarction, or stroke among patients with type 2 diabetes mellitus (T2DM) with and without previous cardiovascular disease (CVD).
The database study designed to emulate the REWIND trial will be a new-user active comparative study, where we compare the effect of dulaglutide vs sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4i), on MACE among patients with T2DM with and without previous CVD. While the REWIND trial compared dulaglutide vs placebo, we chose to use sitagliptin as an active-comparator proxy for placebo. Sitagliptin was specifically chosen because a major randomized controlled trial on cardiovascular outcomes demonstrated that the drug does not affect the cardiovascular outcomes under investigation. Furthermore, clinical guidelines during the study period recommended both drug classes under investigation as second- or third-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 dulaglutide | – | Drug: DulaglutideExposure group |
| Initiation of sitagliptin | – | Drug: SitagliptinReference group |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Two populations: (1) Individuals with T2DM, who are either aged 50 years or above with an established cardiovascular disease, aged 55 years or above with a subclinical cardiovascular disease, or aged 60 years or above with at least two cardiovascular risk factors; and (2) individuals typically treated in clinical practice who are at low, moderate, and high cardiovascular risk with T2DM.
Key inclusion criteria (11 listed)
- MI, Stroke, Revascularization procedure, Diagnosis of coronary/carotid/peripheral artery disease, diagnosis of hypertensive heart disease
- BMI >= 23.0kg/m2
- Type 2 Diabetes Mellitus
- Chronic Kidney Disease (CKD) Stage 3/4
- Albuminuria
Key exclusion criteria (22 listed)
- MEN syndrome or medullary thyroid carcinoma, organ transplant, malignancy
- Severe hypoglycemic episode
- CKD stage 5 or dialysis
- Gastric emptying abnormality or bariatric surgery
- Pregnancy
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 |
|---|---|---|
| DulaglutideInitiation of dulaglutide dispensing claim is used as the exposure. | Drug | Initiation of dulaglutide |
| SitagliptinInitiation of sitagliptin dispensing claim is used as the reference. | Drug | Initiation of sitagliptin |
Primary outcome
Time to first occurrence of myocardial infarction, stroke, or all-cause mortality
Time frame: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
The primary outcome is the time from cohort entry to the first occurrence of any component of the composite endpoint: myocardial infarction, stroke, or all-cause mortality in patients with T2DM with and without previous CVD, comparing dulaglutide versus sitagliptin, when following the eligibility criteria of the REWIND trial.
Time to first occurrence of myocardial infarction, stroke, or all-cause mortality
Time frame: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
The outcome is the time from cohort entry to the first occurrence of any component of the composite endpoint: myocardial infarction, stroke, or all-cause mortality in patients with T2DM with and without previous CVD, comparing dulaglutide versus sitagliptin, when expanding the eligibility criteria of the REWIND trial.
3 secondary outcomes
Time to first occurrence of myocardial infarction, stroke, or all-cause mortality, assessed as individual components
Time frame: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
Time to first occurrence of a heart failure event
Time frame: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
Time to first occurrence of unstable angina
Time frame: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.
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 10 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 Type 2 Diabetes, 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 11 inclusion and 22 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 10 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?
Time to first occurrence of myocardial infarction, stroke, or all-cause mortality (time frame: From cohort entry through first occurrence of outcome, disenrollment, end of the study period, treatment discontinuation +45-day grace/risk window, treatment switch between arms, nursing home admission, start of another GLP-1 RA, assessed up to 1 year.). The study lists 2 primary outcomes in all. 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 10 Jul 2026.