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.
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
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
Parallel
Semaglutide 14 MG [Rybelsus]
DrugSemaglutide 3 mg daily - up-titrated to 7 mg daily if well tolerated - up-titrated to 14 mg daily if well tolerated
Dapagliflozin (Forxiga)
DrugDapagliflozin 10 mg daily
Metformin
DrugMetformin 500 mg daily (up-titrated to 1000 mg daily if indicated)
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
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)
Evaluation of the effect of each of the tested drugs vs. control group on progression of coronary artery disease
% change in volume of noncalcified atherosclerotic plaque assessed by coronary CT (as treated) between baseline and end of study
Comparison of the effect of semaglutide vs. flozin on coronary artery disease progression
% change in volume of noncalcified atherosclerotic plaque assessed by coronary CT (intention to treat/as treated) between baseline and end of study
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
% change in volume of the entire atherosclerotic plaque assessed by coronary CT) (intention to treat/as treated) between baseline and end of study
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
% change in volume of individual components of atherosclerotic plaque assessed by coronary CT (intention to treat/as treated) between baseline and end of study
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National Institute of Cardiology, Warsaw, Poland
Lead sponsor
Medical Research Agency, Poland
Collaborator
