Anti-atherosclerotic Efficacy of Selected Antidiabetic Drugs in Patients With Coronary Artery Disease and Pre-diabetes

NCT ID: NCT07254572

Last Updated: 2025-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-10

Study Completion Date

2029-08-01

Brief Summary

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The purpose of the study is to compare the anti-atherosclerotic efficacy of oral treatment with a GLP-1 analogue (semaglutide) or an SGLT-2 (so-called "flozin") inhibitor (dapagliflozin) versus routine treatment (metformin) in patients with pre-diabetes and diagnosed coronary artery disease at 24 months.

The diagnosis of coronary artery disease will be defined as the presence of coronary atherosclerosis confirmed by coronary artery computed tomography (coronary CT).

The study will evaluate the effect of treatment with flozin vs. semaglutide compared to treatment with metformin on the progression/regression of coronary atherosclerosis, change in plaque character, and control of cardiovascular risk factors.

Detailed Description

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Conditions

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Coronary Artery Disease PreDiabetes

Keywords

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Coronary Artery Disease Prediabetes Coronary Plaque Metformin SGLT-2 GLP-1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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DAPAGLIFLOZIN

Dapagliflozin + OMT \& Lifestyle Intervention

Group Type EXPERIMENTAL

Optimal Medical Therapy (OMT) And Lifestyle Intervention

Intervention Type BEHAVIORAL

* cardiological counselling aiming to reduce risk factors of atherosclerosis progression (LDL target, optimal medical therapy, comorbidities management, electrocardiogram) in accordance with current European Society of Cardiology guidelines
* dietary counselling
* body weight management
* advice on optimizing physical activity levels
* advice on how to quit smoking if applicable
* psychological counselling

Dapagliflozin (Forxiga)

Intervention Type DRUG

Dapagliflozin 10 mg daily

SEMAGLUTIDE

Semaglutide + OMT \& Lifestyle Intervention

Group Type EXPERIMENTAL

Optimal Medical Therapy (OMT) And Lifestyle Intervention

Intervention Type BEHAVIORAL

* cardiological counselling aiming to reduce risk factors of atherosclerosis progression (LDL target, optimal medical therapy, comorbidities management, electrocardiogram) in accordance with current European Society of Cardiology guidelines
* dietary counselling
* body weight management
* advice on optimizing physical activity levels
* advice on how to quit smoking if applicable
* psychological counselling

Semaglutide 14 MG [Rybelsus]

Intervention Type DRUG

Semaglutide 3 mg daily - up-titrated to 7 mg daily if well tolerated - up-titrated to 14 mg daily if well tolerated

METFORMIN

Metformin + OMT \& Lifestyle Intervention

Group Type ACTIVE_COMPARATOR

Optimal Medical Therapy (OMT) And Lifestyle Intervention

Intervention Type BEHAVIORAL

* cardiological counselling aiming to reduce risk factors of atherosclerosis progression (LDL target, optimal medical therapy, comorbidities management, electrocardiogram) in accordance with current European Society of Cardiology guidelines
* dietary counselling
* body weight management
* advice on optimizing physical activity levels
* advice on how to quit smoking if applicable
* psychological counselling

Metformin

Intervention Type DRUG

Metformin 500 mg daily (up-titrated to 1000 mg daily if indicated)

Interventions

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Optimal Medical Therapy (OMT) And Lifestyle Intervention

* cardiological counselling aiming to reduce risk factors of atherosclerosis progression (LDL target, optimal medical therapy, comorbidities management, electrocardiogram) in accordance with current European Society of Cardiology guidelines
* dietary counselling
* body weight management
* advice on optimizing physical activity levels
* advice on how to quit smoking if applicable
* psychological counselling

Intervention Type BEHAVIORAL

Semaglutide 14 MG [Rybelsus]

Semaglutide 3 mg daily - up-titrated to 7 mg daily if well tolerated - up-titrated to 14 mg daily if well tolerated

Intervention Type DRUG

Dapagliflozin (Forxiga)

Dapagliflozin 10 mg daily

Intervention Type DRUG

Metformin

Metformin 500 mg daily (up-titrated to 1000 mg daily if indicated)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age 18 - 80
* Diagnosed coronary artery disease (coronary artery stenosis of at least 20% with a reference diameter of \>2.5 mm or status after percutaneous coronary revascularization procedure found on coronary CT scan)
* Coronary CT scan performed \<3 months after inclusion in the study, at least of good quality
* Pre-diabetic status defined as fasting blood glucose 100-125 mg% or Hba1c 5.70-6.49% (measurement documented at the screening/randomization appointment or within 30 days prior to the screening/randomization appointment) or documented, positive result of an oral glucose load test (fasting blood glucose 100-125 mg% and 140-199 mg% 2h after a 75 g oral glucose load) performed up to 30 days before the screening/randomization appointment
* Stable treatment and control of cardiovascular risk factors, including dietary and lifestyle management for at least 4 weeks
* Willing and able to give informed consent to participate in the study
* Willing and able, according to the researcher, to comply with all the requirements of the study

Exclusion Criteria

* Severe valvular defect
* Clinical condition requiring surgical treatment of coronary artery disease
* Status after coronary artery bypass surgery
* Diagnosed diabetes or Hba1c\>=6.5% at screening/randomization appointment
* Other severe medical conditions requiring scheduled hospital treatment at the time of the study
* Severe musculoskeletal conditions requiring specific rehabilitation recommendations
* Diagnosed heart failure
* Presence of an artificial valve, cardiac pacing system or other implantable device (such as a cardioverter defibrillator)
* Severe arrhythmia/unexplained loss of consciousness
* Other contraindications to physical activity
* No consent to participate in the study
* Use of glucose-lowering drugs other than metformin
* Use of weight-loss drugs
* Condition after bariatric surgery
* Diagnosed liver disease or ALT, AST above three times the upper limit of normal at screening appointment
* Uncompensated hyperthyroidism
* Pancreatic cancer
* Medullary thyroid cancer
* History of anaphylactic shock after iodine contrast administration
* Chronic kidney disease (eGFR \<45 ml/min/1.73 m2)
* History of pancreatitis or active pancreatitis
* Body mass index (BMI) \>40 kg/m2
* Pregnancy/lactation
* Participation in another clinical trial
* Other known contraindications to treatment with metformin, dapagliflozin or semaglutide
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical Research Agency, Poland

OTHER_GOV

Sponsor Role collaborator

National Institute of Cardiology, Warsaw, Poland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jan Henzel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cardiology

Mariusz Kruk, MD, PhD

Role: STUDY_CHAIR

National Institute of Cardiology

Cezary Kępka, MD, PhD

Role: STUDY_CHAIR

National Institute of Cardiology

Locations

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National Institute of Cardiology, Department of Coronary Artery and Structural Heart Diseases

Warsaw, , Poland

Site Status RECRUITING

Countries

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Poland

Central Contacts

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Jan Henzel, MD, PhD

Role: CONTACT

Phone: +48 22 343 43 42

Email: [email protected]

Kinga Kotlinska

Role: CONTACT

Phone: +48 22 343 40 88

Email: [email protected]

Facility Contacts

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Kinga Kotlińska

Role: primary

Agnieszka Nowicka

Role: backup

References

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https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-22/diabetes-total-risk-benefit-of-sglt2-inhibitors-and-glp1-agonists#.ZC8_KhOdj2E.link

Reference Type RESULT

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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CSDS.IV/VIII/2023

Identifier Type: -

Identifier Source: org_study_id