Semaglutide effects on cardiovascular outcomes in people with overweight or obesity (SELECT)

People that are overweight or obese are at high risk for cardiovascular (CV) disease. Semaglutide has shown CV risk reduction and impact on CV risk factors including overweight, dysglycemia and increased blood pressure in subjects with type-2 diabetes. It is not known whether semaglutide will reduce CV disease risk and mortality in subjects with established CV disease and are overweight or obese.

Primary Objective: To demonstrate that semaglutide s.c. 2.4 mg once-weekly lowers the incidence of major adverse cardiovascular events (MACE) versus semaglutide placebo both added to standard of care in subjects with established CV disease and overweight or obesity.

Secondary Objectives: To compare the effect of semaglutide s.c. 2.4 mg once-weekly versus semaglutide placebo both added to standard of care in subjects with established CV disease and overweight or obesity with regards to:

• Mortality
• CV risk factors
• Glucose metabolism
• Body weight
• Renal function

Benefits: In clinical trials semaglutide has provided clinically relevant reductions in body weight as compared to placebo. The CV safety of semaglutide has been established in subjects with type 2 diabetes in a CV outcomes trial (SUSTAIN-6)4 and the trial suggested a clinically relevant cardiovascular risk reduction (ie: heart attack, stroke) with semaglutide compared to placebo. During this trial it is expected that all subjects, including those randomized to placebo will benefit from participation through frequent contact with the trial site, where CV diseases and risk factors are monitored and treated following careful medical examinations. In addition, all subjects will be offered healthy lifestyle counseling. All subjects in this trial will receive trial product and auxiliary supplies free of charge. Patients receive $50 per visit. There are 24 total visits (spaced out initially once/month and then about every 3 months).

Inova Cardiology - Fairfax
8081 Innovation Park Drive, Suite 700
Fairfax, VA 22031

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
2. Male or female, age ≥ 45 years at the time of signing informed consent
3. Body mass index (BMI) ≥ 27 kg/m2
4. Have established CV disease as evidenced by at least one of the following:
   a. prior myocardial infarction
   b. prior stroke (ischemic or hemorrhagic stroke)
   c. symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) < 0.85 (at rest), or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease

All exclusion criteria are based on the subjects’ medical records, except for #4 (HbA1c, central laboratory) and the urine pregnancy test (#17). Subjects are excluded from the trial if any of the following criteria apply:

Cardiovascular-related

• Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischemic attack within the past 60 days prior to the day of screening
• Planned coronary, carotid or peripheral artery revascularization known on the day of screening
• Presently classified as being in New York Heart Association (NYHA) Class IV heart failure

Glycaemia-related

• HbA1c ≥ 48 mmol/mol (6.5%) as measured by the central laboratory at screening
• History of type 1 or type 2 diabetes (history of gestational diabetes is allowed)
• Treatment with glucose-lowering agent(s) within 90 days before screening
• Treatment with any GLP-1 RA within 90 days before screening

General safety

• History or presence of chronic pancreatitis
• Presence of acute pancreatitis within the past 180 days prior to the day of screening
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• End stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening Basal and squamous cell skin cancer and any carcinoma in-situ are allowed
• Severe psychiatric disorder which in the investigator’s opinion could compromise compliance with the protocol
• Known or suspected hypersensitivity to trial product(s) or related products
• Previous participation in this trial. Participation is defined as randomization
• Receipt of any investigational medicinal product within 30 days before screening
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method
• Any disorder, unwillingness or inability, which in the investigator’s opinion might jeopardize the subject’s safety or compliance with the protocol