SEMAGLUTIDE for Type 2 diabetes mellitus

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years."}
• {"criterion_text":"- Diagnosis of T2DM in patients without ASCVD or severe TOD but with SCORE2-Diabetes >=10% with clinical indication in accordance with current guidelines [1] to initiate semaglutide therapy (level of evidence IIa)."}
• {"criterion_text":"- Evaluable, pre-randomization CTA with no evidence of stenosis ≥50% of epicardial coronary vessels, as confirmed by the core laboratory, performed within 2 years prior to inclusion."}
• {"criterion_text":"- Stable clinical conditions, with controlled blood pressure, lipid profile, and glycemic values, based on assessments performed within 4 weeks prior to inclusion."}
• {"criterion_text":"- Stable antidiabetic treatment for at least 6 weeks."}
• {"criterion_text":"- Left ventricular ejection fraction ≥50%."}
• {"criterion_text":"- For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at enrollment by one of the following: (a) Postmenopausal, defined as amenorrhea for ≥12 months following cessation of fall exogenous hormonal treatments, and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range. (b) Documentation of irreversible surgical sterilization by hysterectomy bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization."}
• {"criterion_text":"- Ability to understand study procedures and sign informed consent."}

Exclusion criteria

• {"criterion_text":"- Age > 85 years."}
• {"criterion_text":"- Hypersensitivity to the active substance or to any of the excipients."}
• {"criterion_text":"- Known or suspected liver disease, defined by serum transaminase and alkaline phosphatase levels 3 times the normal level."}
• {"criterion_text":"- Patients with acute inflammatory or infectious diseases during the 3 months prior to inclusion in the study."}
• {"criterion_text":"- Patients with chronic inflammatory, immune or infectious diseases."}
• {"criterion_text":"- Patients with a history of cancer within the past 5 years."}
• {"criterion_text":"- History of alcohol, drug or medication abuse."}
• {"criterion_text":"- Patients exposed to any other type of radiation, medical or professional."}
• {"criterion_text":"- Clinically relevant haematological disorders."}
• {"criterion_text":"- Decompensated metabolic disorders."}
• {"criterion_text":"- Abuse of alcohol or drugs in the previous 3 months."}
• {"criterion_text":"- Previous treatment with semaglutide or GLP1-RAs"}
• {"criterion_text":"- Patients with stenosis of epicardial coronary arteries ≥50%."}
• {"criterion_text":"- eGFR <45 mL/min/1.73 m2 irrespective of albuminuria or eGFR 45– 59 mL/min/1.73 m2 and microalbuminuria (UACR 30–300 mg/g; stage A2) or proteinuria (UACR >300 mg/g; stage A3) or presence of microvascular disease in at least three different sites [e.g. microalbuminuria (stage A2) plus retinopathy plus neuropathy], based on assessments performed within 4 weeks prior to inclusion."}
• {"criterion_text":"- History of any clinically important disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant’s ability to participate in the study."}
• {"criterion_text":"- Any history of ASCVD."}
• {"criterion_text":"- Ongoing New York Heart Association Class IV (heart failure (HF)."}
• {"criterion_text":"- Significant valvulopathy."}
• {"criterion_text":"- Type 1 diabetes mellitus."}

Primary endpoints

• {"endpoint_text":"- To evaluate the effects of semaglutide in addition to standard therapy on inflammatory biomarkers compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes >=10%. Regarding this endopoint, the change in inflammatory biomarkers and biomarkers of endothelial function at follow-up compared to baseline will be evaluated in both treatment arms.","definition_or_measurement_approach":"Change in inflammatory biomarkers and biomarkers of endothelial function at follow-up compared to baseline will be evaluated in both treatment arms."}

Secondary endpoints

• {"endpoint_text":"- To retrospectively evaluate fat attenuation index (FAI) and characteristics of subclinical atherosclerotic coronary plaques at CTA in T2DM patients without history ASCVD or severe TOD but with SCORE2-Diabetes >=10%. Regarding this endpoint, data from CTA, performed according to clinical practice before enrollment, will be recorded. FAI and plaque characteristics, including coronary plaque burden, size and composition will be evaluated retrospectively.","definition_or_measurement_approach":"Retrospective analysis of CTA data performed according to clinical practice prior to enrollment; evaluation of FAI and plaque characteristics including burden, size and composition."}
• {"endpoint_text":"- To correlate FAI and characteristics of subclinical atherosclerotic coronary plaques at CTA in T2DM patients without history ASCVD or severe TOD but with SCORE2-Diabetes 10% to biomarkers evaluated at baseline.","definition_or_measurement_approach":"Correlation analyses between baseline biomarkers and FAI/plaque characteristics measured from pre-randomization CTA."}
• {"endpoint_text":"- To correlate FAI and characteristics of subclinical atherosclerotic coronary plaques at CTA to biomarkers evaluated at 52 weeks and to the occurrence of adverse events in T2DM patients without history ASCVD or severe TOD but with SCORE2-Diabetes >=10% in both treatment arms.","definition_or_measurement_approach":"Correlation analyses between biomarkers at 52 weeks and FAI/plaque characteristics, and association with occurrence of adverse events in both arms."}
• {"endpoint_text":"- To assess the safety and tolerability of semaglutide in addition to standard therapy compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes >/=10%. Concerning this endpoint, incidence of adverse events, serious adverse events, and discontinuation rates will be recorded and analyzed in both treatment arms.","definition_or_measurement_approach":"Recording and analysis of incidence of adverse events, serious adverse events, and discontinuation rates in both treatment arms."}

Italy

Earliest CTIS Part Ii Submission Date

21-07-2025

Latest Decision Or Authorization Date

25-11-2025

Processing Time Days

127

Number Of Sites

2

Number Of Participants

80

Primary sponsor

Full Name

Universita' Degli Studi Di Napoli Federico II

Organisation Type

Educational Institution

Country Of Registered Address

Italy

Contract research organisations

Name

Medical Trials Analysis S.r.l.

Responsibilities

Operational/third-party duties (sponsorDuties codes 1,5,8) - contact rvergura@mtagroup.net

Name

Fullcro S.r.l.

Responsibilities

Operational/third-party duties including biological samples shipment management and other study support (sponsorDuties codes 12,15,6,7) - contact flavio.dellarocca@fullcro.org

Third parties

• {"country":"Italy","full_name":"Medical Trials Analysis S.r.l.","duties_or_roles":"sponsorDuties codes: 1,5,8","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"University Of Bari Aldo Moro","duties_or_roles":"CT scan central reading (sponsorDuties code 15)","organisation_type":"Educational Institution"}
• {"country":"Italy","full_name":"Fullcro S.r.l.","duties_or_roles":"sponsorDuties codes include 12, 15 (biological samples shipment management), 6, 7","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"University Magna Graecia Of Catanzaro","duties_or_roles":"sponsorDuties code 4","organisation_type":"Educational Institution"}