TIRzepatide for the Treatment of Obesity in Patients With Atrial Fibrillation

Last updated: January 12, 2026
Sponsor: The Cleveland Clinic
Overall Status: Active - Recruiting

Phase

2

Condition

Arrhythmia

Obesity

Diabetes Prevention

Treatment

Tirzepatide

Placebo

Clinical Study ID

NCT06802081
24-228
  • Ages 18-80
  • All Genders

Study Summary

This is a single center randomized double blind controlled study of patients (BMI ≥ 27 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Subjects eligible for inclusion in this study must meet all of the following criteria:

  1. Sinus rhythm at randomization

  2. Sustained normal sinus rhythm (or)

  3. Normal sinus rhythm at office visit

  4. Age ≥18 to ≤80 years old

  5. BMI ≥ 27 and ≤60 kg/m2

  6. AFIB criteria:

  7. Must be documented by ECG or monitor.

  8. Must have symptomatic AFIB (Atrial Fibrillation).

  9. In terms of types of AFIB, either paroxysmal AFIB or persistent AFIB.

  10. All anti-diabetic medication (including insulin) must be stable for at least 3months prior to enrollment,

  11. HbA1c ≤10% for patients diagnosed with Type 2 Diabetes Mellitus (T2DM).

  12. Ability and willingness to give themselves the medication, comply with studyrequirements and provide written informed consent.

Exclusion

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for inclusion in this study.

  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/surgeryin 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 ondialysis

  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 sinceparticipation 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 thatcould disqualify the patient from metabolic surgery

  19. Any condition or major illness that, in the investigator's judgment, places thesubject 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 (Multiple Endocrine Neoplasia Type 2)

  22. Current use or any use within the last 6 months of GLP-1/DPP4i (Glucagon-LikePeptide-1/Dipeptidyl Peptidase-4 inhibitor) or GIP (Gastric InhibitoryPolypeptide)/GLP-1

  23. Known hypersensitivity to investigational product due to prior use of GLP-1/DPP4i orGIP/GLP-1

  24. Allergy to medical grade tape or adhesive

  25. Pregnant, breast-feeding or plans to become pregnant

Study Design

Total Participants: 100
Treatment Group(s): 2
Primary Treatment: Tirzepatide
Phase: 2
Study Start date:
April 08, 2025
Estimated Completion Date:
June 01, 2027

Study Description

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≥ 27 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.

Connect with a study center

  • Cleveland Clinic

    Cleveland, Ohio 44195
    United States

    Site Not Available

  • Cleveland Clinic

    Cleveland 5150529, Ohio 5165418 44195
    United States

    Active - Recruiting

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