This is a single center randomized double blind controlled study of patients (BMI\> 30 kg/m2) with obesity and Atrial Fibrillation (AFIB) randomized to Tirzepatide vs. placebo. It is expected that the significant weight loss with Tirzepatide will result in improved control, management, symptom severity, and burden of AFIB at 12 months.

It is estimated that 12 million people in the United States will have AFIB by 2030. The obesity epidemic and all its comorbidities such as hypertension, diabetes and sleep apnea are potent risk factors for AFIB. Weight loss has emerged as a potent treatment for AFIB. This will be a randomized double blind controlled study of patients (BMI\> 30 kg/m2) with obesity and AFIB randomized to Tirzepatide vs. placebo in the Cleveland Clinic Health System. It is expected that the weight loss with Tirzepatide will result in improved control, management, symptom severity, and burden of AFIB at 12 months. Patients who met the initial screening criteria (including presence of at least 1% AF burden during a 2 week monitoring period with an ambulatory cardiac monitor) will be invited for possible enrolment. 100 Patients will then be randomized 1:1 to Tirzepatide group versus placebo and will be followed for 12 months. AFIB burden will be assessed through FDA approved event monitor. All patients will receive standard care for management of risk factors as well as nutrition and life style modification counseling. Management of AFIB including pharmacotherapy, ablation, and direct current cardioversion (DCC) will be at the discretion of Cleveland Clinic's cardiologists. Patients and investigators will be blinded to treatment assignment. Assessment of the primary endpoint will be based on the blinded downloads and interpretation of event monitors. The primary objective of the study is to examine Tirzepetide 10mg once a week vs. placebo on severity and symptom burden of AFIB at 12 months.