Impact of Oral Semaglutide on Platelet Reactivity in Patients with Diabetes Mellitus or Overweight with High Risk or established Cardiovascular Disease: the SEMA-PLAT Study

Prior treatment

• Myocardial infarction, stroke, hospitalization for unstable angina pectoris, transient ischemic attack or other arterial or venous thrombosis within the past 90 days prior to the day of screening
• Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years
• Currently enrolled in a competing randomized trial or less than 30 days since ending another trial with an investigational product or device
• On treatment with anticoagulant agents or with antiplatelets other than aspirin or aspirin and clopidogrel
• Use of any DPP-4 inhibitor, any GLP-1 RA or pramlintide within 30 days prior to screening
• Concomitant or expected chronic use of steroids or non-steroidal anti-inflammatory drugs;

Other illness

• History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
• Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Presence of medical conditions that would make the patient unlikely to compliant with study related procedures
• Known or suspected hypersensitivity to semaglutide or related products;
• Patient has a diagnosis of type 1 DM, or a history of ketoacidosis
• Presence of severe heart failure – systolic or diastolic NYHA Class 4;
• Known severe liver disease

Lab values

• Presence of end stage renal impairment defined as eGFR <15ml/min, chronic or intermittent hemodialysis or peritoneal dialysis

Other

• History or presence of acute or chronic pancreatitis
• Proliferative retinopathy or maculopathy requiring acute treatment
• Women who are pregnant, breast feeding or may be considering pregnancy during the study period

• Cohort 1: Type 2 Diabetes mellitus AND an indication for GLP-1 RA treatment as per the ESC guidelines. Cohort 2: BMI≥30kg/m2 OR BMI≥27 kg/m2 non-diabetic patients AND an indication for GLP-1 RA treatment as per the ESC guidelines, including patients with the presence of at least one weight-related comorbidities (hypertension, dyslipidemia, obstructive sleep apnea), OR established CV disease, defined as prior MI, stroke (ischemic and hemorrhagic stroke), or symptomatic PAD (as evidenced by intermittent claudication with ankle–brachial index <0.85, peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease).
• On treatment with aspirin (81-100 mg/od) alone or aspirin (81-100 mg/od) plus clopidogrel (75mg/od) as per standard of care since at least 14 days before enrolment;
• Male or female aged >45 and <75 years;
• Are willing to be consented and to understand the study requirements, to adhere to study treatments, and complete all assessments and all scheduled visits, per Investigator judgment.
• All women of childbearing potential must agree to use highly effective contraception from the time of informed consent until at least 8 weeks after the last dose of the investigational medicinal product.
• Blood tests not older than 2 months including hemoglobin (Hb), estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).