Searching simple biomarkers to phenotype type 2 diabetic patients and personalize their treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Metabolism [G03], Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

8 Jul 2025 → ongoing

Decision date (initial)

2024-10-09

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministero della Salute (Project code: PNRR-MCNT2-2023-12378096)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess responses to different glucose-lowering treatments - dapagliflozin vs oral semaglutide - in patients with T2D categorized into 2 groups, depending on their prevalent insulin resistance (IR) or prevalent insulin secretion deficit (ISD). The differential responses to therapy will be monitored usig a series of non-canonical (e.g., adiponectin, irisin, serpin B1) or canonical biomarkers (HbA1c, glucagon, GLP-1, GIP, insulin, proinflammatory mediators) or other metabolites potentially detected in metabo-lipidomic analysis

Secondary objectives 1

1. To identify a series of non-canonical (e.g., adiponectin, irisin, serpin B1) or canonical biomarkers (glucagon, GLP-1, GIP, insulin, proinflammatory mediators) or other metabolites potentially detected in metabo-lipidomic analysis that could represent a "signature" of the IR or ISD phenotype identified, in order to implement personalized treatment for certain phenotypes of T2D patients treated with GLP-1RA or SGLT-2is

Conditions and MedDRA coding

type 2 diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Provision of informed consent prior to any study specific procedures
2. Age: 20 – 80 years old
3. Sex: Males and Females
4. Stable therapy with metformin for at least 6 months
5. Suboptimal glycemic control (HbA1c ≥6.5 %)
6. Fasting C-peptide > 1 ng/mL (0.33 nmol/L)
7. Women of childbearing potential must have a negative blood or urine pregnancy test at the baseline visit
8. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 5.9 of the protocol
9. Ability to take oral medications
10. Will and ability to comply with the protocol

Exclusion criteria 19

1. Previous type 1 diabetes or Late-Onset Autoimmune Diabetes of the Adult (LADA) diagnosis, as assessed by medical history
2. Inability to provide informed consent
3. History of diabetic ketoacidosis or hyperosmolar non ketotic coma
4. Concomitant anti-diabetic drugs other than metformin
5. Steroidal therapy within the last 3 months
6. Medications known to significantly impact glucose metabolism (e.g., atypical antipsychotics)
7. GAD-Ab positivity
8. Severe obesity (BMI > 40)
9. Altered levels of amylase and lipase
10. Severe liver dysfunction
11. history of pancreatitis, patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
12. Severe renal dysfunction (eGFR < 25 ml/min/1.73m2)
13. Uncontrolled hypertension
14. Uncontrolled dyslipidemia (total cholesterol > 300 mg/dl and/or LDLc > 200 and/or triglycerides > 500 mg/dl)
15. Known hypersensitivity to the active substance or to any of the excipients in study drug
16. Pregnant or breast-feeding women
17. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrhoeic for at least 12 months to be considered of nonchildbearing potential
18. Treatment with hormonal contraception
19. Frailty in elderly participants aged > 75 years, defined as: severe comorbidities associated with limited life expectancy; or Clinical Frailty Scale (CFS) > 5; or cognitive impairment interfering with treatment adherence.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the differential effects of treatment with semaglutide vs dapagliflozin on metabolic compensation and beta-cell function – measured through glycated hemoglobin (HbA1c)

Secondary endpoints 2

1. To verify the ability of biomarkers to offer a signature for patients’ phenotyping even after treatment with dapagliflozin or semaglutide
2. To verify the ability of biomarkers to guide the more appropriate choice between dapagliflozin or semaglutide treatments in well-distinguished phenotypes of diabetic patients

Investigational products

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

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Andrea Giaccari

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Andrea Giaccari

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 27 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