A multiarm, randomized, open label Clinical study comparing AntiatheroSClerotic efficacy of selected Antidiabetic agents in patients with coronary artery disease and preDiabetES. A randomised clinical trial (CASCADES)

Prior treatment

• Use of weight loss medications
• Other known contraindications to treatment with metformin, dapagliflozin or semaglutide

Other illness

• Severe valvular disease
• Severe diseases of the musculoskeletal system requiring specific rehabilitation recommendations
• Decompensated heart failure
• Severe arrhythmia/unexplained loss of consciousness
• Presence of an artificial valve, cardiac pacing system or other implantable device (e.g. cardioverter-defibrillator)
• Condition after bariatric surgery
• History of pancreatitis or active pancreatitis
• History of anaphylactic shock after administration of iodine contrast
• Medullary thyroid cancer
• Pancreatic cancer
• A clinical condition requiring surgical treatment of coronary artery disease
• Condition after coronary artery bypass surgery
• Other serious illnesses requiring planned hospital treatment during the examination

Lab values

• Use of glucose-lowering medications other than metformin
• Diagnosed liver disease or ALT, AST greater than three times the upper limit of normal at the screening visit
• Chronic kidney disease (GFR <60 ml/min/1.73 m2)
• Diagnosed diabetes or Hba1c>6.5 mg% at the time of screening/randomization visit

Other

• Lack of consent to participate in the study
• Other contraindications to physical exercise
• Decompensated hyperthyroidism
• Participation in another clinical trial
• Body mass index (BMI) >40 kg/m2
• Pregnancy/lactation

• Age 18-80
• Diagnosed coronary artery disease (coronary artery stenosis of at least 20% with a reference diameter of >2.5 mm detected in a coronary CT scan or after percutaneous coronary revascularization)
• Core CT scan performed <3 months after inclusion in the study, of at least good quality
• Prediabetes defined as fasting blood glucose 100-125 mg% or Hba1c 5.70 6.49% (measurement documented during the screening/randomization visit or within 30 days before the screening/randomization visit) or a documented positive result of the oral stress test glucose (fasting blood glucose 100-125 mg% and 140-199 mg% 2 hours after an oral load of 75 g of glucose) performed within 30 days before the screening/randomization visit
• Stable treatment and control of cardiovascular risk factors, including dietary and lifestyle management, for at least 4 weeks.
• Willingness and ability to provide informed consent for participation in the study.
• Capability and willingness, in the opinion of the investigator, to comply with all study requirements