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

NCT07254572 | Recruiting Phase 4 DMC

• 1 other identifier: CSDS.IV/VIII/2023
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease; PreDiabetes

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Evaluation of the effect of GLP-1 analogue treatment on coronary artery disease progression AND Evaluation of the effect of flozin treatment on the progression of coronary artery disease (CO-PRIMARY ENDPOINTS)

  Change in % volume of noncalcified atherosclerotic plaque in the coronary arteries assessed by coronary CT versus routine management (intention-to-treat) AND Change in % volume of noncalcified atherosclerotic plaque in the coronary arteries assessed by coronary CT versus routine management (intention-to-treat)

  24 months

Secondary Outcomes (30)

• Evaluation of the effect of each of the tested drugs vs. control group on progression of coronary artery disease

  24 months

• Comparison of the effect of semaglutide vs. flozin on coronary artery disease progression

  24 months

• Evaluation of the effect of each study drug vs. control group/comparison of the effect of semaglutide vs. flozin on progression of coronary artery disease

  24 months

• Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on progression of coronary artery disease

  24 months

• Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on progression of coronary artery disease (plaque conversion)

  24 months

Study Arms (3)

DAPAGLIFLOZIN

EXPERIMENTAL

Dapagliflozin + OMT \& Lifestyle Intervention

Drug: Dapagliflozin (Forxiga); Behavioral: Optimal Medical Therapy (OMT) And Lifestyle Intervention

SEMAGLUTIDE

EXPERIMENTAL

Semaglutide + OMT \& Lifestyle Intervention

Drug: Semaglutide 14 MG [Rybelsus]; Behavioral: Optimal Medical Therapy (OMT) And Lifestyle Intervention

METFORMIN

ACTIVE COMPARATOR

Metformin + OMT \& Lifestyle Intervention

Drug: Metformin; Behavioral: Optimal Medical Therapy (OMT) And Lifestyle Intervention

Interventions

Semaglutide 14 MG [Rybelsus] DRUG

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

SEMAGLUTIDE

Dapagliflozin (Forxiga) DRUG

Dapagliflozin 10 mg daily

DAPAGLIFLOZIN

Metformin DRUG

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

METFORMIN

Optimal Medical Therapy (OMT) And Lifestyle Intervention 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; METFORMIN; SEMAGLUTIDE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Cardiology, Warsaw, Poland: lead
• Medical Research Agency, Poland: collaborator

Study Sites (1)

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

Warsaw, Poland

RECRUITING

Related Publications (1)

• 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

  RESULT

Related Links

• Study information in Polish

MeSH Terms

Conditions

Coronary Artery Disease; Prediabetic State

Interventions

semaglutide; dapagliflozin; Metformin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Jan Henzel, MD, PhD

  National Institute of Cardiology

  PRINCIPAL INVESTIGATOR

• Mariusz Kruk, MD, PhD

  National Institute of Cardiology

  STUDY CHAIR

• Cezary Kępka, MD, PhD

  National Institute of Cardiology

  STUDY CHAIR

Central Study Contacts

Jan Henzel, MD, PhD

CONTACT

+48 22 343 43 42; jhenzel@ikard.pl

Kinga Kotlinska

CONTACT

+48 22 343 40 88; kkotlinska@ikard.pl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2025
• First Posted: November 28, 2025
• Study Start: July 10, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: November 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)