The Effects of Tirzepatide in People With Overweight/Obesity and Coronary Artery Disease

Inclusion Criteria:

• Informed written consent

• BMI equal to or above 27 kg/m2

• Age 18 years or older

• Referred to coronary angiogram (CAG) due to stable angina

• Coronary atheromatosis by angiography (obstructive or non-obstructive)

• LCBI4mm >200 by NIRS in a vessel not subjected to coronary intervention

Exclusion Criteria:

• History of diabetes or HbA1c ≥48 mmol/mol (6.5%) at baseline

• Treatment with Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA)

• History of coronary artery bypass surgery (CABG)

• Planned CV intervention (including percutaneous coronary intervention, cardiacsurgery or transcatheter valve intervention) at time of randomisation

• History of heart failure New York Heart Association (NYHA) class III or IV

• Left ventricular ejection fraction (LVEF) ≤35%

• eGFR <30 ml/min/1.53 m2

• History of pancreatitis or plasma amylase >2 times upper normal limit

• Impaired hepatic function at baseline (alanine aminotransferase (ALT) or aspartateaminotransferase (AST) >3 times the upper limit of normal)

• Pregnancy, planned pregnancy or breastfeeding

• Family or history of multiple endocrine neoplasia (MEN) type 2 or familial medullarythyroid carcinoma (FMTC)

• Hypersensitivity to the active substance (Tirzepatide) or to any of the excipients

• Left main stenosis (≥50% diameter or haemodynamically significant)

• Chronic total occlusion of any major coronary vessel

• Multi-vessel disease or complex anatomy potentially requiring coronary bypasssurgery

• Coronary anatomy or pathology precluding the safe performance of intravascularimaging in all major coronary arteries not subjected to intervention