Semaglutide for Metabolic Intervention and Adipose Loss to Treat Atrial Fibrillation

Eligibility Criteria

• 1. Age 18-75 years
• 2. BMI greater than or equal to 30 kg/m2
• 3. Paroxysmal AF or persistent AF, in whom catheter ablation (CA) for AF is expected within 1 year (A group) or in whom catheter ablation is NOT expected within 1 year (M group)
• 4. Ability to provide informed consent before any trial-related activities.
• 5. Patients with type 2 diabetes mellitus (T2DM) will be included:
• 1. If HbA1c (glycated hemoglobin) is less than or equal to 10 %
• 2. If the subject is taking basal insulin only or oral hypoglycemic agents or a combination of those.
• 3. Patients on SGLT2-inhibitors and TZDs (Thiazolidinedione) will be included if they have been on a stable dose of these medications for at least 6 months
• 4. The following protocol will be adopted to adjust insulin secretagogues (sulfonylureas or meglitinides) and insulin during the study (adapted from the Look Ahead Study).
• * 2 blood sugars \<100 mg/dl- reduce meds \[insulin secretagogues (sulfonylureas or meglitinides) and basal insulin\] by 0-50 %
• * 3 blood sugars 80-100 mg/dl- reduce meds \[insulin secretagogues (sulfonylureas or meglitinides) and basal insulin\] by 25-75%
• * 3 blood sugars \<80 mg/dl \> 2 x week or severe hypoglycemia or symptomatic hypoglycemia- reduce meds \[insulin secretagogues (sulfonylureas or meglitinides) and basal insulin\] by 50-100 %
• 1. Current use of GLP-1 RA (glucagon-like peptide receptor agonists) or DPP4 (Dipeptidyl peptidase-4)-inhibitors or use within the last 90 days prior to screening
• 2. Current antiobesity medication use or use within the last 90 days prior to screening
• 3. A self-reported change in body weight of \> 5 kg (11 lb.) within 30 days before screening
• 4. History of bariatric surgery
• 5. History of type I diabetes mellitus
• 6. Current use of prandial insulin
• 7. Hospitalization for unstable angina, or TIA (Transient ischemic attack) \< 30 days prior to screening
• 8. Pulmonary embolism \< 90 days before screening
• 9. MI (myocardial infarction), stroke, etc. \< 90 months prior to screening
• 10. Uncontrolled thyroid disease: TSH (Thyroid-stimulating hormone) \> 10.0 mIU/L (Milli-international Units Per Liter) or \< 0.4 mIU/L (Milli-international Units Per Liter) at screening
• 11. Active malignancy
• 12. Active enrollment in another investigational study that includes any kind of intervention
• 13. The receipt of any investigational drug within 90 days prior to this trial.
• 14. Inability to comply with study procedures
• 15. Acute pancreatitis \< 180 days before screening
• 16. History or presence of chronic pancreatitis
• 17. CKD (Chronic Kidney Disease) stage 4 (GFR \<30 ml/min)
• 18. A personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• 19. A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in WEGOVY
• 20. Chronic inflammatory conditions requiring immunosuppression and/or on glucocorticoids
• 21. Previous participation in this trial (received at least one dose of study drug or placebo)
• 22. Pregnant, breast-feeding or planning pregnancy