Diabetes Mellitus, Type 2NCT06659718
Emulation of the SOUL Diabetes Trial in 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?
- Oral semaglutide and Sitagliptin
- Type of treatment
- Pill or oral medicine
- How many people
- 43,650 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2024to 13 Feb 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
- Adult, Older adult
Study population: The study population included patients aged 50 years or older with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).
Who may be able to join
- Type 2 diabetes mellitus
- Male or female, age equal to or above 50 years
- At least one of the following conditions:
- Coronary heart disease defined by at least one of the following criteria:
- Prior myocardial infarction ii. Prior coronary revascularization procedure ii. 50% or above stenosis in coronary artery documented by cardiac catheterization, computerized tomography coronary angiography iv. Coronary heart disease with ischemia documented by stress test with any imaging modality
- Cerebrovascular disease defined by at least one of the following criteria:
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- Prior stroke ii. Prior carotid artery revascularization procedure iii. 50% or above stenosis in carotid artery documented by x-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound
- Symptomatic peripheral artery disease (PAD) defined by at least one of the following criteria:
- Intermittent claudication with an Ankle-brachial index (ABI) below 0.85 at rest ii. Intermittent claudication with a 50% or above stenosis in peripheral artery (excluding carotid) documented by x-ray angiography, magnetic resonance angiography, computerized tomography angiography or Doppler ultrasound iii. Prior peripheral artery(excluding carotid) revascularization procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding trauma or osteomyelitis)
- Chronic kidney disease defined as: i. eGFR below 60mL/min/1.73 m^2 (based on medical records using latest available and no more than 6 months old assessment)
Who cannot join
- Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischemic attack within the past 60 days prior to the day of screening
- Heart failure presently classified as being in New York Heart Association Class IV
- Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before screening
- Semaglutide
- History of MEN-2 or family history of medullary thyroid cancer
- History of pancreatitis
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- History of or planning bariatric surgery, including banding procedures or surgical gastric and/or intestinal bypass
- Plans for pregnancy during the course of the study for women of child-bearing potential
- History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior to randomization
- Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment (corresponding to eGFR <30 ml/min/1.73 m2)
- Proliferative retinopathy or maculopathy requiring acute treatment
- History of diabetic ketoacidosis
- 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 and Established Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease: SOUL 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 SOUL trial, which is a superiority trial to evaluate the effect of oral semaglutide versus placebo on MACE outcomes (CV death, nonfatal MI, or nonfatal stroke) among individuals with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).
The database study designed to emulate SOUL 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 and with established ASCVD and/or CKD. 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
- Oral semaglutide, 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.
Oral semaglutideDrug
New use of oral semaglutide dispensing claim is used as the exposure.
SitagliptinDrug
New initiation of sitagliptin dispensing claim is used as the reference.
| Study group | Role | What they receive |
|---|---|---|
| Oral semaglutide | Exposure group Receives: Drug: Oral semaglutide | |
| Sitagliptin | Reference group Receives: Drug: 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 completion13 Feb 2025
- Study completion13 Feb 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
- 43,650 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
- NCT06659718
- Sponsor's protocol ID
- 2018P002966-DUP-SOUL
- 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 and Established Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease: SOUL Trial
- ClinicalTrials.gov ID
- NCT06659718
- Acronym / sponsor ID
- 2018P002966-DUP-SOUL
- Conditions
- Diabetes Mellitus, Type 2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 43,650 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 24 Oct 2024 (actual)
- Primary completion
- 13 Feb 2025 (actual)
- Study completion
- 13 Feb 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 SOUL trial, which is a superiority trial to evaluate the effect of oral semaglutide versus placebo on MACE outcomes (CV death, nonfatal MI, or nonfatal stroke) among individuals with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).
The database study designed to emulate SOUL 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 and with established ASCVD and/or CKD. 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 |
|---|---|---|
| Oral semaglutide | – | Drug: Oral semaglutideExposure group |
| Sitagliptin | – | Drug: SitagliptinReference group |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- The study population included patients aged 50 years or older with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).
Key inclusion criteria (10 listed)
- Type 2 diabetes mellitus
- Male or female, age equal to or above 50 years
- Coronary heart disease defined by at least one of the following criteria:
- Cerebrovascular disease defined by at least one of the following criteria:
- Symptomatic peripheral artery disease (PAD) defined by at least one of the following criteria:
Key exclusion criteria (14 listed)
- Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischemic attack within the past 60 days prior to the day of screening
- Heart failure presently classified as being in New York Heart Association Class IV
- Treatment with any glucagon-like peptide-1 receptor agonist within 30 days before screening
- Semaglutide
- History of MEN-2 or family history of medullary thyroid cancer
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 |
|---|---|---|
| Oral semaglutideNew use of oral semaglutide dispensing claim is used as the exposure. | Drug | Oral semaglutide |
| SitagliptinNew initiation of sitagliptin dispensing claim is used as the reference. | Drug | 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 10 inclusion and 14 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.