Semaglutide's effects on inflammation and blood vessel health in type 2 diabetes

Impact of GLP1-RAs on Inflammation and Endothelial biomarkerS in Type 2 diABetes meLlitus patiEnts: STABLE-GLP1 Trial

This trial will test whether adding semaglutide to standard treatment reduces inflammation and improves blood vessel function in adults with type 2 diabetes who do not have diagnosed heart disease.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Federico II University (other)
• Drugs / interventions: radiation
• Locations: 2 sites (Caserta, Caserta and 1 other locations)
• Trial ID: NCT07314684 on ClinicalTrials.gov

What this trial studies

The STABLE-GLP1 trial is a phase IV, randomized, pragmatic study enrolling 80 adults with type 2 diabetes but without clinical atherosclerotic cardiovascular disease or severe target-organ damage. Participants are randomized 1:1 to receive semaglutide in addition to guideline-based standard therapy or to continue standard therapy alone. Eligibility requires a recent coronary CTA core-lab read showing no ≥50% epicardial stenosis and stable clinical and laboratory parameters, and the trial will measure inflammatory and endothelial biomarkers alongside clinical prognosis. The multicenter study is conducted in Italy at Federico II University and Azienda Ospedaliera Sant'Anna e San Sebastiano.

Who should consider this trial

Good fit: Adults with type 2 diabetes who have no established ASCVD, a SCORE2-Diabetes ≥10%, a coronary CTA within 2 years showing <50% epicardial stenosis, stable antidiabetic therapy, and LVEF ≥50% are the ideal candidates.

Not a fit: People with established atherosclerotic cardiovascular disease, severe target-organ damage, significant coronary stenosis, unstable clinical conditions, or who are pregnant or breastfeeding are unlikely to be eligible or to benefit from this study.

Why it matters

Potential benefit: If successful, this could show that semaglutide reduces vascular inflammation and improves endothelial function, potentially lowering future cardiovascular risk in people with type 2 diabetes.

How similar studies have performed: Large cardiovascular outcome trials of GLP-1 receptor agonists including semaglutide have shown reductions in major cardiovascular events, but local effects on inflammation and endothelial biomarkers remain less well studied.

Eligibility 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:

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%.
* 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.

Where this trial is running

Caserta, Caserta and 1 other locations

• Azienda Ospedaliera Sant'Anna e San Sebastiano — Caserta, Caserta, Italy (RECRUITING)
• Federico II University — Naples, Napoli, Italy (RECRUITING)

Conditions: T2DM, Type 2 Diabetes Mellitus, Semaglutide, Inflammation, Endothelial function, Biomarkers, Coronary Plaque