OverweightNCT07141914
A Master Protocol for Semaglutide Effects on Cardiovascular and Obesity-related Outcomes in People With Overweight or Obesity in the Real World
An observational study of Overweight and Obesity, run by Novo Nordisk A/S at 1 site in United States.
Trial summary
This study aims to evaluate the association of once-weekly semaglutide with the risk of cardiovascular (CV) and other obesity-related clinical outcomes in three study populations (Heart failure (HF), clinical Atherosclerotic Cardiovascular Disease (ASCVD), primary prevention). Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Overweight, Obesity, Heart Failure (HF)
- What is being tested?
- No treatment given
- How many people
- 285,327 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Aug 2025to 19 Dec 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 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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
- 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
- Smoking history
- Dyslipidaemia
- Hypertension
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- Prediabetes
- Chronic kidney disease (CKD) or evidence of kidney function decline/kidney damage
- 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
Who cannot join
- 1. Population specific exclusion criteria:
- HF and Clinical ASCVD Populations: Diagnosis of end-stage HF
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Novo Nordisk Investigational
Plainsboro, New Jersey, 08536
About this study
This study aims to evaluate the association of once-weekly semaglutide with the risk of cardiovascular (CV) and other obesity-related clinical outcomes in three study populations (Heart failure (HF), clinical Atherosclerotic Cardiovascular Disease (ASCVD), primary prevention).
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.
- Conditions
- Overweight, Obesity, Heart Failure (HF), Atherosclerotic Cardiovascular Disease (ASCVD), Primary Prevention
- Being tested
- No treatment given
- Medical subject headings
- Overweight, Obesity, Heart Failure, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No treatment givenOther
No treatment given
No treatment givenOther
No treatment given
| Study group | Role | What they receive |
|---|---|---|
| Cohort: Semaglutide users | Not described Receives: Other: No treatment given | |
| Cohort: Semaglutide Non-users | Not described Receives: Other: No treatment given |
What is being measured
The primary outcome is the main question the study is designed to answer.
Revised 5-Point Major Adverse Cardiovascular Events (MACE-5) (time-to-event)
Measured as Months
Occurrence of any of the following individual component events:
- Myocardial infarction (MI)
- Stroke
- Hospitalization for HF
- Coronary revascularization (including coronary artery bypass grafting and percutaneous coronary intervention)
- All-cause mortality
The event date will be the earliest occurrence of one of the individual components.
Measured: Index date, earliest of revised MACE-5 and end of follow-up; up to 42 months
Revised 3-point Major Adverse Cardiovascular Events MACE-3 (time-to-event)
Measured in Months
Occurrence of any of the following individual component events:
- MI
- Stroke
- All-cause mortality
The event date will be the earliest occurrence of one of the individual components.
Measured: Index date, earliest of revised MACE-3 and end of follow-up; up to 42 months
Secondary outcomes (11)
MI (time-to-event)
Measured as Months
A primary diagnosis of MI (identified using International Classification of Disease, 10th Edition, Clinical Modification (ICD-10-CM) diagnosis codes observed during an inpatient (IP) visit).
The event date will be admission date of the IP visit.
Measured: Index date, earliest of MI and end of follow-up; up to 42 months
Stroke (time-to-event)
Measured as Months
A primary diagnosis of stroke, including both ischemic and haemorrhagic, (identified using ICD-10-CM diagnosis codes observed during an IP visit).
The event date will be the admission date of the IP visit.
Measured: Index date, earliest of stroke and end of follow-up; up to 42 months
Hospitalization for HF (time-to-event)
Measured as Months
A primary diagnosis of HF (identified using ICD-10-CM diagnosis codes observed during an IP visit).
The event date will be the first observed admission date of the IP visit.
Measured: Index date, earliest of hospitalization for HF and end of follow-up; up to 42 months
Coronary revascularization (time-to-event)
Measured as Months
Evidence of coronary revascularization in any claim (identified using International Classification of Disease, 10th Edition, Procedure Coding System (ICD-10-PCS), Current Procedural Terminology (CPT), or Healthcare Common Procedure Coding System (HCPCS) procedure codes).
The event date will be the first observed date of coronary revascularization.
Measured: Index date, earliest of Coronary revascularization and end of follow-up; up to 42 months
All-cause mortality (time-to-event)
Measured as Months
Evidence of death as recorded at the month and year level in Komodo Research Data (KRD) and defined as a death record observed within the last month of follow-up.
The event date will be the earliest of the end of follow-up (e.g., bariatric surgery within the month of death and last month of follow-up) or the last day of the recorded month of death.
Measured: Index date, end of follow-up; up to 42 months
MACE-5 (time-to-event)
Measured as Months
Occurrence of any of the following individual component events:
- MI
- Stroke
- Hospitalization for HF
- Coronary revascularization
- CV-related mortality
The event date will be the earliest occurrence of one of the individual components.
Measured: Index date, earliest of MACE-5 and end of follow-up; up to 42 months
MACE-3 (time-to-event)
Measured as Months
Occurrence of any of the following individual component events:
- MI
- Stroke
- CV-related mortality
The event date will be the earliest occurrence of one of the individual components.
Measured: Index date, earliest of MACE-3 and end of follow-up; up to 42 months
CV-related mortality (time-to-event)
Measured as Months
Any claim within ≤30 days before the date of death (i.e. the last day of the recorded month of death, where death is observed in the last month of follow- up) of the following operational definition to indicate CV related mortality:
- Primary diagnosis of MI
- Primary diagnosis of ischemic or haemorrhagic stroke
- Primary diagnosis of HF
- Evidence of aortic or peripheral arterial revascularization, coronary revascularization, or carotid revascularization or intervention in any claim
- Primary diagnosis of CV haemorrhage (excluding haemorrhagic stroke)
- Primary diagnosis of other CV conditions including unstable angina, sudden cardiac arrest, cardiogenic shock, \& other cerebrovascular \& CV events Non-CV-related mortality is defined as all other records of death that are not classified as CV-related mortality.
The event date will be the earliest of the end of follow-up (e.g. bariatric surgery within the month of death) or the date of death.
Measured: Index date, end of follow-up; up to 42 months
Urgent HF visit (time-to-event)
Measured as Months
A primary diagnosis of HF (identified using ICD-10-CM diagnosis codes observed during a non-IP visit). Further, at least one the following interventions must be observed in a non-IP claim on the same day as the non-IP visit:
- Procedure indicating administration of intravenous diuretics or vasoactive agents (identified using HCPCS procedure codes)
- Pharmacy claim for an intravenous diuretic or vasoactive agent (identified using National Drug Codes (NDCs))
- Diagnosis of an encounter for mechanical circulatory support or mechanical fluid removal or dependence on dialysis (identified using ICD-10-CM diagnosis codes)
- Procedure for mechanical circulatory support or mechanical fluid removal (identified using ICD-10- PCS, CPT, and HCPCS procedure codes)
The event date will be the first observed date of the non-IP visit that meets the urgent HF criteria.
Measured: Index date, earliest of urgent HF visit and end of follow-up; up to 42 months
3-point HF (time-to-event)
Measured as Months
Occurrence of any of the following individual component events:
- Hospitalization for HF
- Urgent HF visit
- CV-related mortality
The event date will be the earliest occurrence of one of the individual components.
Measured: Index date, earliest of 3-point HF composite outcome and end of follow-up; up to 42 months
2-point HF (time-to-event)
Measured as Months
Occurrence of any of the following individual component events:
- Hospitalization for HF
- Urgent HF visit
The event date will be the earliest occurrence of one of the individual components.
Measured: Index date, earliest of 2-point HF composite outcome and end of follow-up; up to 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2025
- Study start29 Aug 2025
- Primary completion19 Dec 2025
- Study completion19 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OverweightStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe 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
- 285,327 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Transparency dept. 2834, Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07141914
- Sponsor's protocol ID
- NN9536-8669
- Other IDs
- U1111-1326-1795
- Status last verified
- Jan 2026
- First submitted
- 15 Aug 2025
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Master Protocol for Semaglutide Effects on Cardiovascular and Obesity-related Outcomes in People With Overweight or Obesity in the Real World
- ClinicalTrials.gov ID
- NCT07141914
- Acronym / sponsor ID
- NN9536-8669
- Conditions
- Overweight, Obesity, Heart Failure (HF), Atherosclerotic Cardiovascular Disease (ASCVD), Primary Prevention
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 285,327 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 29 Aug 2025 (actual)
- Primary completion
- 19 Dec 2025 (actual)
- Study completion
- 19 Dec 2025 (actual)
- First posted
- 26 Aug 2025 (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.
This study aims to evaluate the association of once-weekly semaglutide with the risk of cardiovascular (CV) and other obesity-related clinical outcomes in three study populations (Heart failure (HF), clinical Atherosclerotic Cardiovascular Disease (ASCVD), primary prevention).
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort: Semaglutide users | – | Other: No treatment given |
| Cohort: Semaglutide Non-users | – | Other: No treatment given |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (13 listed)
- 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
- 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
- Smoking history
- Dyslipidaemia
Key exclusion criteria (11 listed)
- HF and Clinical ASCVD Populations: Diagnosis of end-stage HF
- 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
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 |
|---|---|---|
| No treatment givenNo treatment given | Other | Cohort: Semaglutide users |
| No treatment givenNo treatment given | Other | Cohort: Semaglutide Non-users |
Primary outcome
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
Measured as Months Occurrence of any of the following individual component events: 1. Myocardial infarction (MI) 2. Stroke 3. Hospitalization for HF 4. Coronary revascularization (including coronary artery bypass grafting and percutaneous coronary intervention) 5. All-cause mortality The event date will be the earliest occurrence of one of the individual components.
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
Measured in Months Occurrence of any of the following individual component events: 1. MI 2. Stroke 3. All-cause mortality The event date will be the earliest occurrence of one of the individual components.
11 secondary outcomes
MI (time-to-event)
Time frame: Index date, earliest of MI and end of follow-up; up to 42 months
Stroke (time-to-event)
Time frame: Index date, earliest of stroke and end of follow-up; up to 42 months
Hospitalization for HF (time-to-event)
Time frame: Index date, earliest of hospitalization for HF and end of follow-up; up to 42 months
Coronary revascularization (time-to-event)
Time frame: Index date, earliest of Coronary revascularization and end of follow-up; up to 42 months
All-cause mortality (time-to-event)
Time frame: Index date, end of follow-up; up to 42 months
MACE-5 (time-to-event)
Time frame: Index date, earliest of MACE-5 and end of follow-up; up to 42 months
MACE-3 (time-to-event)
Time frame: Index date, earliest of MACE-3 and end of follow-up; up to 42 months
CV-related mortality (time-to-event)
Time frame: Index date, end of follow-up; up to 42 months
Urgent HF visit (time-to-event)
Time frame: Index date, earliest of urgent HF visit and end of follow-up; up to 42 months
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
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
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 23 Jan 2026.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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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.
Clinical Transparency dept. 2834 study director
Novo Nordisk A/S
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 Overweight and Obesity, run by Novo Nordisk A/S 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 13 inclusion and 11 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 23 Jan 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?
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). 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 23 Jan 2026.