GLP1-RAs Effects on Inflammatory and Endothelial Biomarkers in T2DM

NCT07314684 | Recruiting Phase 4 DMC

• 2 other identifiers: P2022TF9AH2025-520802-37-00
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Type II diabetes mellitus (T2DM) is a chronic disease associated with a very high risk of developing cardiovascular (CV) events, especially because of its long-term effects. Glucagon-like-peptide-1 receptor agonists (GLP1-RAs) are recommended in subjects suffering from T2DM with a history or at risk for CV disease; however there is a lack of evidence on local actions of GLP1-RAs on inflammation and endothelial function. The STABLE-GLP1 study aims to evaluate, in patients with T2DM without atherosclerotic cardiovascular disease (ASCVD) or severe target-organ damage (TOD), the possible beneficial effect of semaglutide, a GLP1-AR, on clinical prognosis, inflammatory and endothelial biomarkers. The STABLE-GLP1 trial is a phase IV interventional, national, multicenter, randomized, pragmatic study, aiming at enrolling 80 patients with T2DM and no ASCVD. Participants will be randomized in 1:1 ratio to receive semaglutide in addition to standard therapy or standard therapy alone, according to body mass index (BMI) category (BMI \<30 vs. ≥30 kg/m²). All patients will perform clinical visit, ECG, echocardiography, blood sample collection for endothelial and inflammatory biomarkers dosage at baseline, at 26 weeks, and after 52 weeks of treatment. Data from CTA, performed according to clinical practice before enrollment, will be recorded and retrospectively evaluated to test secondary outcomes.

Conditions

T2DM (Type 2 Diabetes Mellitus)

Keywords

Type 2 Diabetes Mellitus; Semaglutide; Inflammation; Endothelial function; Biomarkers; Coronary Plaque

Outcome Measures

Primary Outcomes (2)

• 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 endpoint, the change in inflammatory biomarkers involved in atherogenesis at follow-up compared to baseline will be evaluated in both treatment arms. Inflammatory biomarkers will be measured in serum using an appropriately validated immunoassay (ELISA - enzyme-linked immunosorbent assay). Inflammatory biomarkers include C-reactive protein (CRP), interleukins (IL-1β, IL-6, IL-10), colony-stimulating factors (M-CSF), tumor necrosis factors (TNF-α), interferons (IFN-γ), transforming growth factors (TGF-β), and adiponectin, all measured in picograms per milliliter (pg/mL).

  From enrollment to the end of treatment at 52 weeks

• To evaluate the effects of semaglutide in addition to standard therapy on biomarkers of endothelial dysfunction compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.

  Regarding this endpoint, the change in biomarkers involved in endothelial dysfunction at follow-up compared to baseline will be evaluated in both treatment arms. Biomarkers of endothelial dysfunction will be measured in serum using an appropriately validated immunoassay (ELISA - enzyme-linked immunosorbent assay), and include soluble endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin, all measured in nanograms per milliliter (ng/mL).

  From enrollment to the end of treatment at 52 weeks

Secondary Outcomes (9)

• To retrospectively evaluate fat attenuation index (FAI) at CTA in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.

  At baseline retrospectively

• To retrospectively evaluate characteristics of subclinical atherosclerotic coronary plaques at CTA in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.

  At baseline retrospectively

• To correlate FAI in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10% to biomarkers evaluated at baseline.

  At baseline

• To correlate characteristics of subclinical atherosclerotic coronary plaques at CTA in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10% to biomarkers evaluated at baseline.

  At baseline

• To correlate FAI at CTA to biomarkers evaluated at 52 weeks in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.

  From enrollment to the end of treatment at 52 weeks

Other Outcomes (1)

• To evaluate the effect of semaglutide in addition to standard therapy on time to MACE compared with standard therapy alone in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10%.

  From enrollment to the end of treatment at 52 weeks

Study Arms (2)

Semaglutide in addition to standard therapy

EXPERIMENTAL

Drug: semaglutide; Drug: Standard Treatment (Guideline-Based)

Standard therapy alone

EXPERIMENTAL

Drug: Standard Treatment (Guideline-Based)

Interventions

semaglutide DRUG

The starting dose is 0.25 mg semaglutide once weekly. After 4 weeks the dose should be increased to 0.5 mg once weekly. After at least 4 weeks with a dose of 0.5 mg once weekly, the dose can be increased to 1 mg once weekly to further improve glycaemic control.

Semaglutide in addition to standard therapy

Standard Treatment (Guideline-Based) DRUG

Patients will receive standard therapy for T2DM according to standard clinical practice (Guideline-Based). This might include Biguanides, Insulins, Sulfonylureas, SGLT2 inhibitors, Thiazolidinediones, Alpha-glucosidase inhibitors, or DPP-4 inhibitors.

Semaglutide in addition to standard therapy; Standard therapy alone

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Age \> 85 years.
• Previous treatment with semaglutide or GLP1-RAs.
• Patients with stenosis of epicardial coronary arteries ≥50%.
• 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 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.

Sponsors & Collaborators

• Federico II University: lead

Study Sites (2)

Azienda Ospedaliera Sant'Anna e San Sebastiano

Caserta, Caserta, 81100, Italy

RECRUITING

Federico II University

Naples, Napoli, 80131, Italy

RECRUITING

Related Publications (1)

• Marx N, Federici M, Schutt K, Muller-Wieland D, Ajjan RA, Antunes MJ, Christodorescu RM, Crawford C, Di Angelantonio E, Eliasson B, Espinola-Klein C, Fauchier L, Halle M, Herrington WG, Kautzky-Willer A, Lambrinou E, Lesiak M, Lettino M, McGuire DK, Mullens W, Rocca B, Sattar N; ESC Scientific Document Group. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023 Oct 14;44(39):4043-4140. doi: 10.1093/eurheartj/ehad192. No abstract available.

  PMID: 37622663 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Endpoint assessment and statistical analysis will be performed by personnel blinded to treatment assignment to reduce the risk of bias in data interpretation. In addition, the Events Adjudication Committee will be composed of at least three board-certified cardiologists, who are not involved in the conduct of the trial and are blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Phase IV low-interventional, Italian, multicenter, randomized, pragmatic clinical trial

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: January 2, 2026
• Study Start: September 8, 2025
• Primary Completion (Estimated): March 8, 2027
• Study Completion (Estimated): March 8, 2027
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)