Impact of GLP1-RAs on inflammation and endothelial biomarkerS in Type 2 diABetes meLlitus patiEnts: STABLE-GLP1 trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita' Degli Studi Di Napoli Federico II

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2025-09-09

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

PRIN 2022 PNRR financing fund

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

- 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%.

Secondary objectives 4

1. 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%.
2. 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.
3. 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.
4. To assess the safety and tolerability of semaglutide in addition to standard therapy compared with standard therapy alone in T2DM patients T2DM patients without ASCVD or severe TOD but with SCORE2-Diabetes >/=10%.

Conditions and MedDRA coding

Type 2 diabetes mellitus

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age ≥ 18 years.
2. 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).
3. 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.
4. Stable clinical conditions, with controlled blood pressure, lipid profile, and glycemic values, based on assessments performed within 4 weeks prior to inclusion.
5. Stable antidiabetic treatment for at least 6 weeks.
6. Left ventricular ejection fraction ≥50%.
7. 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.
8. Ability to understand study procedures and sign informed consent.

Exclusion criteria 19

1. Age > 85 years.
2. Previous treatment with semaglutide or GLP1-RAs
3. Patients with stenosis of epicardial coronary arteries ≥50%.
4. 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.
5. 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.
6. Any history of ASCVD.
7. Ongoing New York Heart Association Class IV (heart failure (HF).
8. Significant valvulopathy.
9. Type 1 diabetes mellitus.
10. Hypersensitivity to the active substance or to any of the excipients.
11. Known or suspected liver disease, defined by serum transaminase and alkaline phosphatase levels 3 times the normal level.
12. Patients with acute inflammatory or infectious diseases during the 3 months prior to inclusion in the study.
13. Patients with chronic inflammatory, immune or infectious diseases.
14. Patients with a history of cancer within the past 5 years.
15. History of alcohol, drug or medication abuse.
16. Patients exposed to any other type of radiation, medical or professional.
17. Clinically relevant haematological disorders.
18. Decompensated metabolic disorders.
19. Abuse of alcohol or drugs in the previous 3 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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 endopoint, the change in inflammatory biomarkers and biomarkers of endothelial function at follow-up compared to baseline will be evaluated in both treatment arms.

Secondary endpoints 4

1. 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.
2. 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.
3. 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.
4. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita' Degli Studi Di Napoli Federico II

Sponsor organisation

Universita' Degli Studi Di Napoli Federico II

Address

Via Sergio Pansini 5

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

Universita' Degli Studi Di Napoli Federico II

Contact name

Paola Gargiulo

Public contact point

Organisation

Universita' Degli Studi Di Napoli Federico II

Contact name

Paola Gargiulo

Third parties 4

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications