TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation

Eligibility Criteria

• 1. Sinus rhythm at enrollment
• 1. Sustained normal sinus rhythm for 2 hours following cardioversion (or)
• 2. Normal sinus rhythm at office visit or post ablation (at least 6 months post ablation)
• 2. Age ≥18 to ≤80 years old
• 3. BMI \>30 and ≤60 kg/m2
• 4. AFIB criteria:
• 1. Must be documented by ECG or monitor.
• 2. Must have symptomatic AFIB.
• 3. In terms of types of AFIB, either paroxysmal AFIB or persistent AFIB.
• 5. All anti-diabetic medication (including insulin) must be stable for at least 3 months prior to enrollment,
• 6. HbA1c ≤10% for patients diagnosed with Type 2 Diabetes Mellitus (T2DM).
• 7. Ability and willingness to give themselves the medication, comply with study requirements and provide written informed consent.
• 1. AFIB ablation within the last 6 months
• 2. Planned ablation prior to 3 months post randomization
• 3. Significant cardiac valvular disease with planned cardiac valve intervention/surgery in the next 12 months
• 4. Severe uncompensated cardiopulmonary disease
• 5. New York Heart Association Class III or IV
• 6. Left ventricular ejection fraction \<35% at the time of screening
• 7. Hospitalization in the past 6 months for myocardial infarction, unstable angina, stroke, transient ischemic attack, or heart surgery
• 8. History of solid organ transplant
• 9. Type 1 diabetes mellitus or auto-immune diabetes
• 10. Estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73 m2 at screening or on dialysis
• 11. Advanced and decompensated cirrhosis characterized by: presence of fibrosis stage 4 (cirrhosis) in liver biopsy, ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.
• 12. Hemoglobin less than 9 g/dL
• 13. Current participation or use of investigational therapy or less than 3 months since participation in any drug or device trial.
• 14. Liver transaminase level \>300 U/L
• 15. Subject reports alcohol use of on average \>2 drinks/day
• 16. Presence of active malignancy (except non-melanoma skin cancer)
• 17. Life expectancy less than 3 years due to concomitant diseases
• 18. Major mental health, psychological disorders, or substance abuse disorders that could disqualify the patient from metabolic surgery
• 19. Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study
• 20. Plans to move outside the primary location of study (Northeast Ohio) within the next 12 months
• 21. Any personal or family history of pancreatitis or medullary thyroid cancer or MEN2
• 22. Current use or any use within the last 6 months of GLP-1/DPP4i or GIP/GLP-1
• 23. Known hypersensitivity to investigational product due to prior use of GLP-1/DPP4i or GIP/GLP-1
• 24. Allergy to medical grade tape or adhesive
• 25. Pregnant, breast-feeding or plans to become pregnant