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

Official title

A Randomized, Open-label, Clinical Trial Evaluating the Anti-atherosclerotic Efficacy of Selected Antidiabetic Drugs in Patients With Coronary Artery Disease and Pre-diabetes

Overview

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.

Interventions

• Drug 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
• Drug Dapagliflozin (Forxiga)
  Dapagliflozin 10 mg daily
• Drug Metformin
  Metformin 500 mg daily (up-titrated to 1000 mg daily if indicated)
• Behavioral 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

Primary outcome measures

• 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) [Time frame: 24 months]

Secondary outcome measures (12)

• Evaluation of the effect of each of the tested drugs vs. control group on progression of coronary artery disease [Time frame: 24 months]
• Comparison of the effect of semaglutide vs. flozin on coronary artery disease progression [Time frame: 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 [Time frame: 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 [Time frame: 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) [Time frame: 24 months]
• Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on CV risk expressed as the dynamics of high-risk features [Time frame: 24 months]
• Evaluation of the effect of each of the tested drugs vs. control group/comparison of the effect of semaglutide vs. flozin on CV risk on pericoronary fat attenuation index [Time frame: 24 months]
• Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - body weight [Time frame: 24 months]
• Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - body mass index [Time frame: 24 months]
• Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - total body fat [Time frame: 24 months]
• Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - body cell mass [Time frame: 24 months]
• Evaluation of changes in anthropometric measurements in patients treated with semaglutide vs. patients treated with flozin - fat to mass ratio [Time frame: 24 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Poland · 1 center

• National Institute of Cardiology, Department of Coronary Artery and Structural Heart Disea — Warsaw

Publications

• 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

Identifiers

NCT: NCT07254572 · CSDS.IV/VIII/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗