GLP1-RAs Effects on Inflammatory and Endothelial Biomarkers in T2DM
ConditionT2DM (Type 2 Diabetes Mellitus)
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-85
SponsorFederico II University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
semaglutide
DrugThe 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.
Standard Treatment (Guideline-Based)
DrugPatients 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.
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Semaglutide in addition to standard therapyExperimental treatment 2 interventions
Group B: Standard therapy aloneExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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).
Time frame
From enrollment to the end of treatment at 52 weeks2
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).
Time frame
From enrollment to the end of treatment at 52 weeksSecondary outcomes
1
To retrospectively evaluate fat attenuation index (FAI) at CTA in T2DM patients without 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 will be evaluated retrospectively using dedicated software and measured in Hounsfield Units (HU).
Time frame
At baseline retrospectively2
To retrospectively evaluate characteristics of subclinical atherosclerotic coronary plaques at CTA in T2DM patients without 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. Coronary plaque size will be evaluated retrospectively using dedicated software and measured as a percentage (%).
Time frame
At baseline retrospectively3
To correlate FAI in T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes ≥10% to biomarkers evaluated at baseline.
Data from CTA, performed according to clinical practice before enrollment, will be recorded. This outcome measure evaluates the correlation between FAI (measured in Hounsfield Units) at CTA and circulating biomarkers measured at baseline (ng/mL or pg/mL). Correlation will be assessed using Pearson or Spearman correlation coefficients, as appropriate.
Time frame
At baseline4
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.
Data from CTA, performed according to clinical practice before enrollment, will be recorded. This outcome measure evaluates the correlation between coronary plaque size (%) at CTA and circulating biomarkers measured at baseline (ng/mL or pg/mL). Correlation will be assessed using Pearson or Spearman correlation coefficients, as appropriate.
Time frame
At baselineOther 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%.
Concerning this endpoint, time from randomization to first occurrence of an expanded MACE endpoint consisting of CV death, non-fatal myocardial infarction (MI) (acute MI only), non-fatal stroke (including ischaemic, haemorrhagic and undetermined stroke), unstable angina, or hospitalization for urgent coronary revascularization, will be analyzed in both treatment arms. All events will be determined by an event adjudication committee (EAC).
Time frame
From enrollment to the end of treatment at 52 weeksSponsors and contacts
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Source ClinicalTrials.gov