TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation

Prior treatment

• Planned ablation prior to 3 months post randomization
• Current participation or use of investigational therapy or less than 3 months since participation in any drug or device trial.
• Life expectancy less than 3 years due to concomitant diseases
• Current use or any use within the last 6 months of GLP-1/DPP4i (Glucagon-Like Peptide-1/Dipeptidyl Peptidase-4 inhibitor) or GIP (Gastric Inhibitory Polypeptide)/GLP-1
• Known hypersensitivity to investigational product due to prior use of GLP-1/DPP4i or GIP/GLP-1

Other illness

• Significant cardiac valvular disease with planned cardiac valve intervention/surgery in the next 12 months
• Severe uncompensated cardiopulmonary disease
• New York Heart Association Class III or IV
• Hospitalization in the past 6 months for myocardial infarction, unstable angina, stroke, transient ischemic attack, or heart surgery
• History of solid organ transplant
• Type 1 diabetes mellitus or auto-immune diabetes
• Advanced and decompensated cirrhosis characterized by: presence of fibrosis stage 4 (cirrhosis) in liver biopsy, ascites, hepatic encephalopathy, portal hypertension, or esophageal varices.
• Presence of active malignancy (except non-melanoma skin cancer)
• Major mental health, psychological disorders, or substance abuse disorders that could disqualify the patient from metabolic surgery
• Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study
• Any personal or family history of pancreatitis or medullary thyroid cancer or MEN2 (Multiple Endocrine Neoplasia Type 2)
• Allergy to medical grade tape or adhesive

Lab values

• Left ventricular ejection fraction \<35% at the time of screening
• Estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73 m2 at screening or on dialysis
• Hemoglobin less than 9 g/dL
• Liver transaminase level \>300 U/L

Other

• Subjects meeting any of the following criteria are not eligible for inclusion in this study.
• AFIB ablation within the last 6 months
• Subject reports alcohol use of on average \>2 drinks/day
• Plans to move outside the primary location of study (Northeast Ohio) within the next 12 months
• Pregnant, breast-feeding or plans to become pregnant

• Subjects eligible for inclusion in this study must meet all of the following criteria:
• Sinus rhythm at randomization
  • Sustained normal sinus rhythm (or)
  • Normal sinus rhythm at office visit
• Age ≥18 to ≤80 years old
• BMI ≥ 27 and ≤60 kg/m2
• AFIB criteria:
  • Must be documented by ECG or monitor.
  • Must have symptomatic AFIB (Atrial Fibrillation).
  • In terms of types of AFIB, either paroxysmal AFIB or persistent AFIB.
• All anti-diabetic medication (including insulin) must be stable for at least 3 months prior to enrollment,
• HbA1c ≤10% for patients diagnosed with Type 2 Diabetes Mellitus (T2DM).
• Ability and willingness to give themselves the medication, comply with study requirements and provide written informed consent.