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

NCT07141914 | Completed

• 2 other identifiers: NN9536-8669U1111-1326-1795
• Study Type: observational
• Target: 285,327
• Locations: 1 country
• Sites: 1

Brief 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). 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); Primary Prevention; Atherosclerotic Cardiovascular Disease (ASCVD)

Outcome Measures

Primary Outcomes (2)

• Revised 5-Point Major Adverse Cardiovascular Events (MACE-5) (time-to-event)

  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.

  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: 1. MI 2. Stroke 3. All-cause mortality The event date will be the earliest occurrence of one of the individual components.

  Index date, earliest of revised MACE-3 and end of follow-up; up to 42 months

Secondary Outcomes (11)

• MI (time-to-event)

  Index date, earliest of MI and end of follow-up; up to 42 months

• Stroke (time-to-event)

  Index date, earliest of stroke and end of follow-up; up to 42 months

• Hospitalization for HF (time-to-event)

  Index date, earliest of hospitalization for HF and end of follow-up; up to 42 months

• Coronary revascularization (time-to-event)

  Index date, earliest of Coronary revascularization and end of follow-up; up to 42 months

• All-cause mortality (time-to-event)

  Index date, end of follow-up; up to 42 months

Study Arms (2)

Cohort: Semaglutide users

Other: No treatment given

Cohort: Semaglutide Non-users

Other: No treatment given

Interventions

No treatment given OTHER

No treatment given

Cohort: Semaglutide users

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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
• \. 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
• 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)
• \. Participants who are more than or equal to (≥) 45 years old by December 31, 2024
• \. 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)
• \. Participant with continuous insurance enrolment eligibility more than or equal to (≥) 12 months prior to the index date (the baseline period)
• \. Participants with re-confirmed overweight/obesity indication during the baseline period

You may not qualify if:

• HF and Clinical ASCVD Populations: Diagnosis of end-stage HF
• Primary Prevention Population: Diagnosis of HF or haemorrhagic stroke, or evidence of clinical ASCVD
• \. Participants with a diagnosis of chronic or acute pancreatitis
• \. Participants with a diagnosis of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• \. Participants with end-stage kidney disease (ESKD) including chronic or intermittent haemodialysis or peritoneal dialysis and/or kidney transplant
• \. More than or equal to (≥ 2) diagnoses of cancer (excluding non-melanoma skin cancer)
• \. Pregnancy in female participants
• \. 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 (%)
• \. 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
• \. Participants with evidence of bariatric surgery

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (1)

Novo Nordisk Investigational

Plainsboro, New Jersey, 08536, United States

Location

MeSH Terms

Conditions

Overweight; Obesity; Heart Failure; Atherosclerosis

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Clinical Transparency dept. 2834

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2025
• First Posted: August 26, 2025
• Study Start: August 29, 2025
• Primary Completion: December 19, 2025
• Study Completion: December 19, 2025
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)