← Trials/Trial dossier/NCT07141914

Completed

A Master Protocol for Semaglutide Effects on Cardiovascular and Obesity-related Outcomes in People With Overweight or Obesity in the Real World

Lead sponsor

Novo Nordisk A/S

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

NCT IDNCT07141914
Org study IDNN9536-8669
Secondary IDU1111-1326-1795World Health Organization (WHO)

Timeline

Milestones

Study first posted2025-08-26actual
Study start2025-08-29actual
Primary completion2025-12-19actual
Study completion2025-12-19actual
Last update posted2026-01-23actual

Assets

Investigational agents

Study populations

Who this study enrolls

Cardiovascular diseaseHeart failureObesity / overweight

Eligibility

Who can enroll

Minimum age45 Years
SexAll
Healthy volunteersNot accepted
Sampling methodNon probability sample

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
Heart failure
4

Cardiovascular outcomes

9 endpoints
Primary/protocol endpoint

Revised 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

Primary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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 endpoints
Secondary/protocol endpoint

Hospitalization 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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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

Secondary/protocol endpoint

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 identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableno registry results posted yet

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.