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A Master Protocol for Semaglutide Effects on Cardiovascular and Obesity-related Outcomes in People With Overweight or Obesity in the Real World
Lead sponsor
Asset
Semaglutide
GLP-1 agonist
Listed sites
1
Recruiting sites
—
Enrollment
285,327
actual
Study population
Cardiovascular disease, Heart failure, Obesity / overweight
Key I/E criterion
—
Primary endpoints
•5-point MACE (Myocardial infarction (any), Stroke (any), Heart-failure hospitalization, Coronary revascularization)•Expanded / custom MACE composite (Myocardial infarction (any), Stroke (any), All-cause death)
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Study population text
This study aims to evaluate the association of once-weekly semaglutide with the risk of CV and other obesity-related clinical outcomes in three study populations. This is a retrospective cohort study which includes administrative medical and pharmacy claims linked with clinical and laboratory measurements for participants in the US during January 1, 2016 - December 31, 2024.
Inclusion criteria
1. Participants with overweight or obesity defined as at least one overweight/obesity indication of a specified body mass index (BMI) more than or equal to (≥) 27.0 kilogram per meter square (kg/m2) and undefined obesity indications, defined by diagnoses and laboratory values, during January 1, 2016 to December 31, 2024
2. Participants with a record indicating the study population of interest during January 1, 2016 to December 31, 2024
1. HF: Diagnosis of HF 2. Clinical ASCVD: Diagnosis or procedure codes indicating:Coronary artery disease (CAD) including acute coronary syndrome (ACS; i.e., myocardial infarction [MI] or unstable angina), stable angina, coronary or other arterial revascularization or intervention, ischemic stroke, transient ischemic attack (TIA), carotid or other arterial stenosis, peripheral arterial disease (PAD) including aortic aneurysm 3. Primary Prevention: Patients at risk for developing ASCVD defined as the presence of more than or equal to (≥) 3 of the following risk factors
1. Smoking history
2. Dyslipidaemia
3. Hypertension
4. Prediabetes
5. Chronic kidney disease (CKD) or evidence of kidney function decline/kidney damage
6. High-sensitivity C-reactive protein (hs-CRP) more than or equal to (≥) 2 milligram per litre (mg/L)
3. Participants who are more than or equal to (≥) 45 years old by December 31, 2024
4. Participants will be divided into the following groups: those who initiate semaglutide on or after the eligibility date and June 4, 2021 (semaglutide users; date of initiation termed the index date) or participants with no evidence of semaglutide usage during January 1, 2016 to December 31, 2024 (non-users; a randomly selected date with ≥ 1 pharmacy claim on or after the eligibility date and June 4, 2021 will be termed the index date)
5. Participant with continuous insurance enrolment eligibility more than or equal to (≥) 12 months prior to the index date (the baseline period)
6. Participants with re-confirmed overweight/obesity indication during the baseline period
Exclusion criteria
1. Population specific exclusion criteria:
1. HF and Clinical ASCVD Populations: Diagnosis of end-stage HF
2. Primary Prevention Population: Diagnosis of HF or haemorrhagic stroke, or evidence of clinical ASCVD
2. Participants with a diagnosis of chronic or acute pancreatitis
3. Participants with a diagnosis of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
4. Participants with end-stage kidney disease (ESKD) including chronic or intermittent haemodialysis or peritoneal dialysis and/or kidney transplant
5. More than or equal to (≥ 2) diagnoses of cancer (excluding non-melanoma skin cancer)
6. Pregnancy in female participants
7. Evidence of diabetes including more than or equal to (≥) 2 diagnoses of type 1 diabetes or more than or equal to (≥) 2 diagnoses of type 2 diabetes on distinct dates, use of a glucose-lowering agent, and/or glycated haemoglobin (HbA1c) laboratory result more than or equal to ≥ 6.5 percent (%)
8. Use of a glucagon-like peptide-1 (GLP-1) or GLP-1/gastric inhibitory polypeptide (GIP) receptor agonist approved for weight management during the baseline period
9. Participants with evidence of bariatric surgery
Endpoints (13)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Cardiovascular outcomes
9 endpointsRevised 5-Point Major Adverse Cardiovascular Events (MACE-5) (time-to-event)
Time frame:Index date, earliest of revised MACE-5 and end of follow-up; up to 42 months
5-point MACE
time to event, event
componentsMyocardial infarction (any), Stroke (any), Heart-failure hospitalization, Coronary revascularization, All-cause death
Revised 3-point Major Adverse Cardiovascular Events MACE-3 (time-to-event)
Time frame:Index date, earliest of revised MACE-3 and end of follow-up; up to 42 months
Expanded / custom MACE composite
time to event, event
componentsMyocardial infarction (any), Stroke (any), All-cause death
MI (time-to-event)
Time frame:Index date, earliest of MI and end of follow-up; up to 42 months
Myocardial infarction (any)
time to event, event
SNOMED 22298006
Stroke (time-to-event)
Time frame:Index date, earliest of stroke and end of follow-up; up to 42 months
Stroke (any)
time to event, event
SNOMED 230690007
Coronary revascularization (time-to-event)
Time frame:Index date, earliest of Coronary revascularization and end of follow-up; up to 42 months
Coronary revascularization
time to event, event
SNOMED 415070008
All-cause mortality (time-to-event)
Time frame:Index date, end of follow-up; up to 42 months
All-cause death
time to event, event
SNOMED 419620001
MACE-5 (time-to-event)
Time frame:Index date, earliest of MACE-5 and end of follow-up; up to 42 months
5-point MACE
time to event, event
componentsMyocardial infarction (any), Stroke (any), Heart-failure hospitalization, Coronary revascularization, Cardiovascular death
MACE-3 (time-to-event)
Time frame:Index date, earliest of MACE-3 and end of follow-up; up to 42 months
3-point MACE
time to event, event
componentsCardiovascular death, Non-fatal MI, Non-fatal stroke
CV-related mortality (time-to-event)
Time frame:Index date, end of follow-up; up to 42 months
Cardiovascular death
time to event, event
Heart failure
4 endpointsHospitalization for HF (time-to-event)
Time frame:Index date, earliest of hospitalization for HF and end of follow-up; up to 42 months
Heart-failure hospitalization
time to event, event
SNOMED 84114007
Urgent HF visit (time-to-event)
Time frame:Index date, earliest of urgent HF visit and end of follow-up; up to 42 months
Urgent heart-failure visit
time to event, event
SNOMED 84114007
3-point HF (time-to-event)
Time frame:Index date, earliest of 3-point HF composite outcome and end of follow-up; up to 42 months
Heart-failure composite
time to event, event
componentsHeart-failure hospitalization, Urgent heart-failure visit, Cardiovascular death
2-point HF (time-to-event)
Time frame:Index date, earliest of 2-point HF composite outcome and end of follow-up; up to 42 months
Heart-failure composite
time to event, event
componentsHeart-failure hospitalization, Urgent heart-failure visit
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.