Semaglutide for Type 2 diabetes mellitus|Cardiovascular disease|Overweight|Obesity

Inclusion criteria

• {"criterion_text":"- 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).\n- 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;\n- Male or female aged >45 and <75 years;\n- 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.\n- 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.\n- Blood tests not older than 2 months including hemoglobin (Hb), estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)."}

Exclusion criteria

• {"criterion_text":"- 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\n- History or presence of acute or chronic pancreatitis\n- 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)\n- Proliferative retinopathy or maculopathy requiring acute treatment\n- Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years\n- Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma\n- Currently enrolled in a competing randomized trial or less than 30 days since ending another trial with an investigational product or device\n- Presence of medical conditions that would make the patient unlikely to compliant with study related procedures\n- Women who are pregnant, breast feeding or may be considering pregnancy during the study period\n- On treatment with anticoagulant agents or with antiplatelets other than aspirin or aspirin and clopidogrel\n- Use of any DPP-4 inhibitor, any GLP-1 RA or pramlintide within 30 days prior to screening\n- Known or suspected hypersensitivity to semaglutide or related products;\n- Concomitant or expected chronic use of steroids or non-steroidal anti-inflammatory drugs;\n- Patient has a diagnosis of type 1 DM, or a history of ketoacidosis\n- Presence of severe heart failure – systolic or diastolic NYHA Class 4;\n- Presence of end stage renal impairment defined as eGFR <15ml/min, chronic or intermittent hemodialysis or peritoneal dialysis\n- Known severe liver disease"}

Primary endpoints

• {"endpoint_text":"- Change in platelet reactivity assessed by light transmission aggregometry [LTA] following ADP (2 and 5 μmol/L) and collagen (2 μg/mL) stimuli between groups at T3;","definition_or_measurement_approach":"Platelet reactivity measured by light transmission aggregometry (LTA) after stimulation with ADP (2 and 5 μmol/L) and collagen (2 μg/mL) comparing groups at timepoint T3."}

Secondary endpoints

• {"endpoint_text":"- Changes between groups at different time points (T1, T2 and T3) in: • Markers of thrombus formation (T-TAS AUC, P-selectin, aGPIIbIIIa, PDMP) • Inflammatory markers (IL-1, IL-6); • Oxidative stress markers (H₂O₂, sNOX2-dp, HBA); • Endothelial function markers (NO, endothelin-1); • Autophagy markers (p62, LC3, ATG5).","definition_or_measurement_approach":"Between-group comparisons at timepoints T1, T2 and T3 for listed biomarker panels: thrombus formation (T-TAS AUC, P-selectin, aGPIIbIIIa, PDMP), inflammatory markers (IL-1, IL-6), oxidative stress (H₂O₂, sNOX2-dp, HBA), endothelial function (NO, endothelin-1), and autophagy markers (p62, LC3, ATG5)."}

Italy

Earliest CTIS Part Ii Submission Date

15-04-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

8

Number Of Sites

1

Number Of Participants

212

Primary sponsor

Full Name

Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy