Diabetes Mellitus, Type 2NCT06659679
Emulating the PIONEER6 Diabetes Trial Using Healthcare Claims
An observational study of Diabetes Mellitus, Type 2, 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
- Diabetes Mellitus, Type 2
- What is being tested?
- New use of oral semaglutide and New initiation of sitagliptin
- Type of treatment
- Pill or oral medicine
- How many people
- 26,126 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2024to 6 Mar 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population includes patients with Type 2 Diabetes (Type2DM), >=50 years with established cardiovascular disease OR >=60 years with subclinical cardiovascular disease.
Who may be able to join
- Type 2 diabetes mellitus
- Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease: prior myocardial infarction, prior stroke or prior transient ischemic attack, prior coronary, carotid or peripheral arterial revascularization, more than 50% stenosis on angiography or imaging of coronary, carotid or lower extremities arteries, chronic heart failure - New York Heart Association (NYHA) class II-III, chronic renal impairment documents by estimated eGFR <60ml/min/1.73 m2 per MDRD
- Age 60 years or older with subclinical evidence of cardiovascular disease. Subclinical cardiovascular risk factors as one of the following: persistent microalbuminuria (30-299mg/g) or proteinuria, ankle/brachial index less than 0.9
Who cannot join
- Type 1 diabetes mellitus, secondary or gestational diabetes
- Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening
- Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening
- History of diabetic ketoacidosis, chronic pancreatitis or idiopathic acute pancreatitis
- Any of the following: myocardial infarction, stroke, or hospitalization for unstable angina or transient ischemic attack within the past 60 days prior to screening
- Chronic heart failure New York Heart Association (NYHA) class IV
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- Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma
- Chronic hemodialysis or peritoneal dialysis
- End stage liver disease
- A prior solid organ transplant or awaiting solid organ transplant
- Diagnosis of malignant neoplasm in the previous 5 years
- Female of childbearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using an adequate contraceptive method
- Proliferative retinopathy or maculopathy requiring treatment
- History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
- Missing age or gender
- Nursing home admission
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: Emulation of the Effects of Oral Semaglutide on Cardiovascular Outcomes in Individuals With Type 2 Diabetes: PIONEER6 Trial
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 RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to emulate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly emulated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not emulable 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 PIONEER6 trial, is a is a non-inferiority trial to evaluate the effects of oral semaglutide versus placebo in terms of cardiovascular safety (CV death, nonfatal MI, or nonfatal stroke) in patients with type 2 diabetes.
The database study designed to emulate PIONEER6 will be a new-user active comparative study, where we compare the effect of oral semaglutide versus sitagliptin on MACE outcome among patients with T2DM. Sitagliptin was selected to act as an active-comparator proxy for placebo. Sitagliptin and the class of dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated not to have an effect on MACE in a series of RCTs, and they are used in similar stages of disease/line of therapy as semaglutide, as well as being similarly costly.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- New use of oral semaglutide, New initiation of 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.
New use of oral semaglutideDrug
New use of oral semaglutide dispensing claim is used as the exposure.
New initiation of sitagliptinDrug
New use of sitagliptin dispensing claim is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| New use of oral semaglutide | Exposure group Receives: Drug: New use of oral semaglutide | |
| New use of sitagliptin | Reference group Receives: Drug: New initiation of sitagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major adverse cardiac event (MACE), including myocardial infarction, stroke, and all cause death
Hazard ratio
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 posted26 Oct 2024
- Study start24 Oct 2024
- Primary completion6 Mar 2025
- Study completion6 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 26,126 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 Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06659679
- Sponsor's protocol ID
- 2018P002966-DUP-PIONEER
- Status last verified
- May 2025
- First submitted
- 24 Oct 2024
- Last updated
- 25 May 2025
- 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 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emulation of the Effects of Oral Semaglutide on Cardiovascular Outcomes in Individuals With Type 2 Diabetes: PIONEER6 Trial
- ClinicalTrials.gov ID
- NCT06659679
- Acronym / sponsor ID
- 2018P002966-DUP-PIONEER
- Conditions
- Diabetes Mellitus, Type 2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26,126 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 24 Oct 2024 (actual)
- Primary completion
- 6 Mar 2025 (actual)
- Study completion
- 6 Mar 2025 (actual)
- First posted
- 26 Oct 2024 (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 RCT DUPLICATE initiative (www.rctduplicate.org) of the Brigham and Women's Hospital, Harvard Medical School. It is intended to emulate, as closely as is possible in healthcare insurance claims data, the trial listed below/above. Although many features of the trial cannot be directly emulated in healthcare claims, key design features, including outcomes, exposures, and inclusion/exclusion criteria, were selected to proxy those features from the trial. Randomization is also not emulable 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 PIONEER6 trial, is a is a non-inferiority trial to evaluate the effects of oral semaglutide versus placebo in terms of cardiovascular safety (CV death, nonfatal MI, or nonfatal stroke) in patients with type 2 diabetes.
The database study designed to emulate PIONEER6 will be a new-user active comparative study, where we compare the effect of oral semaglutide versus sitagliptin on MACE outcome among patients with T2DM. Sitagliptin was selected to act as an active-comparator proxy for placebo. Sitagliptin and the class of dipeptidyl peptidase-4 (DPP-4) inhibitors have been demonstrated not to have an effect on MACE in a series of RCTs, and they are used in similar stages of disease/line of therapy as semaglutide, as well as being similarly costly.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| New use of oral semaglutide | – | Drug: New use of oral semaglutideExposure group |
| New use of sitagliptin | – | Drug: New initiation of sitagliptinReference group |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes patients with Type 2 Diabetes (Type2DM), >=50 years with established cardiovascular disease OR >=60 years with subclinical cardiovascular disease.
Key inclusion criteria (3 listed)
- Type 2 diabetes mellitus
- Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease: prior myocardial infarction, prior stroke or prior transient ischemic attack, prior coronary, carotid or peripheral arterial revascularization, more than 50% stenosis on angiography or imaging of coronary, carotid or lower extremities arteries, chronic heart failure - New York Heart Association (NYHA) class II-III, chronic renal impairment documents by estimated eGFR <60ml/min/1.73 m2 per MDRD
- Age 60 years or older with subclinical evidence of cardiovascular disease. Subclinical cardiovascular risk factors as one of the following: persistent microalbuminuria (30-299mg/g) or proteinuria, ankle/brachial index less than 0.9
Key exclusion criteria (16 listed)
- Type 1 diabetes mellitus, secondary or gestational diabetes
- Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening
- Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening
- History of diabetic ketoacidosis, chronic pancreatitis or idiopathic acute pancreatitis
- Any of the following: myocardial infarction, stroke, or hospitalization for unstable angina or transient ischemic attack within the past 60 days prior to screening
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 |
|---|---|---|
| New use of oral semaglutideNew use of oral semaglutide dispensing claim is used as the exposure. | Drug | New use of oral semaglutide |
| New initiation of sitagliptinNew use of sitagliptin dispensing claim is used as the reference. | Drug | New use of sitagliptin |
Primary outcome
Major adverse cardiac event (MACE), including myocardial infarction, stroke, and all cause death
Time frame: Through study completion (1 day after cohort entry date until the first of outcome or censoring)
Hazard ratio
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 25 May 2025.
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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
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, 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 3 inclusion and 16 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 25 May 2025. 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 cardiac event (MACE), including myocardial infarction, stroke, and all cause death (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?
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 25 May 2025.