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

Novo Nordisk

Status: Completed

Conditions: Atherosclerotic Cardiovascular Disease (ASCVD); Overweight; Heart Failure (HF); Primary Prevention; Obesity

Treatments: Other: No treatment given

Study type: Observational

Funder types: Industry

Identifiers

NCT07141914

U1111-1326-1795 (Other Identifier)

NN9536-8669

Details and patient eligibility

About

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.

Enrollment: 285,327 patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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

Trial design

285,327 participants in 2 patient groups

Cohort: Semaglutide users

Treatment:

Other: No treatment given

Other: No treatment given

Cohort: Semaglutide Non-users

Treatment:

Other: No treatment given

Other: No treatment given