Evaluation of Semaglutide on Inflammatory and Endothelial Biomarkers in Type 2 Diabetes Mellitus Patients Without ASCVD or Severe Target Organ Damage
- Trial ID
- 2025-520802-37-00
- Protocol
- STABLE-GLP1
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to evaluate the effects of **semaglutide** in addition to standard therapy on inflammatory biomarkers compared with standard therapy alone in patients with **Type 2 diabetes mellitus** (T2DM) who do not have a history of atherosclerotic cardiovascular disease (ASCVD) or severe target organ damage (TOD) but have a SCORE2-Diabetes of 10% or higher. This is clinically relevant as it aims to determine the potential benefits of semaglutide in reducing inflammation, which is a key factor in the progression of cardiovascular complications in T2DM patients.
Secondary objectives include:
- Retrospectively evaluating the fat attenuation index (FAI) and characteristics of subclinical atherosclerotic coronary plaques at coronary computed tomography angiography (CTA) in T2DM patients without a history of ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.
- Correlating FAI and characteristics of subclinical atherosclerotic coronary plaques at CTA with biomarkers evaluated at baseline in the same patient population.
- Correlating FAI and characteristics of subclinical atherosclerotic coronary plaques at CTA with biomarkers evaluated at 52 weeks and the occurrence of adverse events in both treatment arms.
- Assessing 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%.
Participants
The clinical trial involves participants diagnosed with **Type 2 diabetes mellitus** (T2DM) who are without atherosclerotic cardiovascular disease (ASCVD) or severe target organ damage (TOD) but have a SCORE2-Diabetes of 10% or higher. The study population includes both male and female subjects aged 18 years and older. Participants are required to have stable clinical conditions, with controlled blood pressure, lipid profile, and glycemic values, and must be on stable antidiabetic treatment for at least six weeks prior to inclusion. Female participants must be of non-childbearing potential. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria ensure that participants have a left ventricular ejection fraction of 50% or higher and an evaluable pre-randomization CTA with no evidence of significant stenosis in epicardial coronary vessels. Participants must be able to understand study procedures and provide informed consent. Lifestyle considerations such as diet and physical activity are not specified in the provided data.
Plans and Procedures
The clinical trial is designed to evaluate the effects of **semaglutide**, a GLP-1 receptor agonist, on inflammatory biomarkers in patients with **Type 2 diabetes mellitus** (T2DM) who do not have atherosclerotic cardiovascular disease (ASCVD) or severe target organ damage (TOD) but have a SCORE2-Diabetes of 10% or higher. This trial is a randomized, double-blind, controlled study, categorized as a low-intervention clinical trial. The trial is expected to commence recruitment in September 2025 and conclude by September 2027, with an estimated duration of 52 weeks for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of T2DM, and stable clinical conditions. The inclusion visit will also ensure that participants have a stable antidiabetic treatment regimen and meet specific cardiovascular health criteria. Following the screening, participants will be randomized to receive either semaglutide in addition to standard therapy or standard therapy alone. The trial will include regular follow-up visits to monitor the effects of the treatment on inflammatory biomarkers and to assess the safety and tolerability of semaglutide. These visits will also involve the collection of data on the fat attenuation index (FAI) and characteristics of subclinical atherosclerotic coronary plaques via computed tomography angiography (CTA).
The end-of-study visit will evaluate the primary endpoint, which is the change in inflammatory biomarkers and biomarkers of endothelial function from baseline to follow-up. Secondary endpoints include the retrospective evaluation of FAI and coronary plaque characteristics, as well as the correlation of these factors with biomarkers and adverse events. Participant involvement is expected to last for the full duration of the trial unless early termination is warranted due to adverse events, non-compliance with study procedures, or withdrawal of consent. The trial aims to provide valuable insights into the potential benefits of semaglutide in managing inflammation and cardiovascular risk in T2DM patients.
Treatment
The clinical trial involves the administration of **semaglutide**, a **GLP-1 receptor agonist**, as the experimental medication. Semaglutide is provided in the form of a **solution for injection** and is administered using a pre-filled syringe. The trial includes three different dosing regimens of semaglutide. The first regimen involves a maximum daily dose of 0.5 mg, administered for a treatment period of up to 48 weeks. The second regimen consists of a maximum daily dose of 0.25 mg, with a treatment duration of up to 4 weeks. The third regimen involves a maximum daily dose of 1 mg, administered for a treatment period of up to 44 weeks. Each dosing regimen is designed to evaluate the effects of semaglutide on inflammatory biomarkers in patients with Type 2 Diabetes Mellitus (T2DM) without atherosclerotic cardiovascular disease (ASCVD) or severe target organ damage (TOD) but with a SCORE2-Diabetes of 10% or higher.
In addition to the experimental treatment, participants will continue to receive standard-of-care therapy for T2DM, which serves as the comparator treatment in this study. The standard therapy is not specified in the trial data but typically includes lifestyle modifications and other antidiabetic medications as per clinical guidelines. The trial aims to assess the impact of semaglutide in conjunction with standard therapy compared to standard therapy alone.
Participant compliance with the dosing schedule will be monitored throughout the trial. The administration of semaglutide via pre-filled syringes is intended to ensure accurate dosing and ease of use. The trial does not involve any pediatric formulations, and semaglutide is not classified as an orphan drug in this study. The trial's objective is to provide insights into the potential benefits of semaglutide on inflammation and endothelial biomarkers in the specified patient population.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the effects of **semaglutide** in addition to standard therapy on inflammatory biomarkers compared with standard therapy alone in patients with Type 2 Diabetes Mellitus (T2DM) without Atherosclerotic Cardiovascular Disease (ASCVD) or severe Target Organ Damage (TOD) but with a SCORE2-Diabetes of 10% or higher. The primary endpoint involves measuring the change in inflammatory biomarkers and biomarkers of endothelial function at follow-up compared to baseline in both treatment arms.
Secondary endpoints include the retrospective evaluation of the fat attenuation index (FAI) and characteristics of subclinical atherosclerotic coronary plaques at Coronary Computed Tomography Angiography (CTA) in the specified patient population. 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. Additionally, correlations between FAI, plaque characteristics, and biomarkers evaluated at baseline and at 52 weeks will be assessed, along with the occurrence of adverse events. The safety and tolerability of semaglutide in addition to standard therapy will also be assessed by recording and analyzing the incidence of adverse events, serious adverse events, and discontinuation rates in both treatment arms.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 years.
- 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).
- 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.
- Stable clinical conditions, with controlled blood pressure, lipid profile, and glycemic values, based on assessments performed within 4 weeks prior to inclusion.
- Stable antidiabetic treatment for at least 6 weeks.
- Left ventricular ejection fraction ≥50%.
- 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.
- Ability to understand study procedures and sign informed consent.
Exclusion Criteria
- Age > 85 years.
- Previous treatment with semaglutide or GLP1-RAs
- Patients with stenosis of epicardial coronary arteries ≥50%.
- 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.
- 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.
- Any history of ASCVD.
- Ongoing New York Heart Association Class IV (heart failure (HF).
- Significant valvulopathy.
- Type 1 diabetes mellitus.
- Hypersensitivity to the active substance or to any of the excipients.
- Known or suspected liver disease, defined by serum transaminase and alkaline phosphatase levels 3 times the normal level.
- Patients with acute inflammatory or infectious diseases during the 3 months prior to inclusion in the study.
- Patients with chronic inflammatory, immune or infectious diseases.
- Patients with a history of cancer within the past 5 years.
- History of alcohol, drug or medication abuse.
- Patients exposed to any other type of radiation, medical or professional.
- Clinically relevant haematological disorders.
- Decompensated metabolic disorders.
- Abuse of alcohol or drugs in the previous 3 months.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 01 Sept 2025 | 80 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
SEMAGLUTIDE | Test | — | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | 0.25 | 4 | SUB32188 |
SEMAGLUTIDE | Test | — | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | 1 | 44 | SUB32188 |
SEMAGLUTIDE | Test | — | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | 0.5 | 48 | SUB32188 |