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

National Institute of Cardiology, Warsaw, Poland

Status and phase: Enrolling; Phase 4

Conditions: Coronary Artery Disease; PreDiabetes

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07254572

CSDS.IV/VIII/2023

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

300 participants in 3 patient groups

DAPAGLIFLOZIN

Experimental group

Description:

Dapagliflozin + OMT \& Lifestyle Intervention

Treatment:

Drug: Dapagliflozin (Forxiga)

Behavioral: Optimal Medical Therapy (OMT) And Lifestyle Intervention

SEMAGLUTIDE

Experimental group

Description:

Semaglutide + OMT \& Lifestyle Intervention

Treatment:

Drug: Semaglutide 14 MG [Rybelsus]

Behavioral: Optimal Medical Therapy (OMT) And Lifestyle Intervention

METFORMIN

Active Comparator group

Description:

Metformin + OMT \& Lifestyle Intervention

Treatment:

Behavioral: Optimal Medical Therapy (OMT) And Lifestyle Intervention

Drug: Metformin