Can Mounjaro Cause Atrial Fibrillation?
Mounjaro (tirzepatide) is not a recognized cause of atrial fibrillation based on current evidence, and it does not appear in established guidelines or reviews of drug-induced atrial fibrillation.
Evidence from Drug-Induced AF Literature
The most comprehensive and recent guideline on drug-induced atrial fibrillation (2024) extensively reviews cardiovascular and non-cardiovascular drugs that can trigger AF, with particular emphasis on anticancer drugs 1. Tirzepatide is notably absent from this comprehensive review, which specifically catalogs drugs known to cause drug-induced AF (DIAF) 1.
The guideline identifies specific drug classes that genuinely cause AF 1:
- Anticancer drugs (particularly ibrutinib with 3-16% incidence, immune checkpoint inhibitors, and tyrosine kinase inhibitors) 1
- Class IC antiarrhythmic drugs (flecainide, propafenone) that can paradoxically convert AF to atrial flutter with dangerous 1:1 AV conduction 2
- Class IA and III antiarrhythmic drugs associated with QT prolongation and torsades de pointes 2
Tirzepatide's Actual Safety Profile
Recent real-world safety data from 65,974 FAERS reports (2022-2025) identified the most common adverse events with tirzepatide 3:
- Incorrect dose administration (most frequent, with 9,800 cases in 2024)
- Injection-site reactions (5,273 cases of pain in 2024)
- Gastrointestinal issues (nausea in 3,602 cases in 2024)
- Class-related effects (decreased appetite, blood glucose fluctuations)
Atrial fibrillation was not identified as a safety signal in this comprehensive post-marketing surveillance analysis 3.
Indirect Cardiac Risk: Electrolyte Disturbances
The only documented cardiac arrhythmia risk with tirzepatide involves severe electrolyte imbalances from gastrointestinal side effects, not direct AF causation 4. A 2025 case report described ventricular fibrillation (not atrial fibrillation) in a patient on high-dose tirzepatide (15 mg weekly) who developed:
- Profound vomiting and diarrhea
- Critical electrolyte depletion (K⁺ 2.2, Mg²⁺ 1.1, corrected Ca²⁺ 5.6)
- Resulting ventricular fibrillation and cardiac arrest 4
This represents an indirect mechanism through volume depletion and electrolyte loss, not a direct pro-arrhythmic drug effect 4.
Cardiovascular Benefits in Heart Failure
Contrary to causing arrhythmias, tirzepatide demonstrated cardiovascular benefits in the 2025 SUMMIT trial involving 731 patients with heart failure with preserved ejection fraction 5:
- Reduced composite endpoint of cardiovascular death or worsening heart failure (9.9% vs 15.3%, HR 0.62) 5
- Improved quality of life scores 5
- No signal for increased arrhythmias despite 104 weeks median follow-up 5
Clinical Monitoring Recommendations
If a patient on tirzepatide develops atrial fibrillation, investigate standard AF risk factors rather than attributing it to the medication 1:
- Structural heart disease (hypertension, left atrial enlargement, coronary artery disease, heart failure, valvular disease) 1
- Non-cardiac comorbidities (diabetes, hyperthyroidism, obesity, sleep apnea, chronic kidney disease) 1
- Acute precipitants (excessive alcohol, surgery, pericarditis, myocarditis, pulmonary embolism) 1
- Other medications that genuinely cause DIAF 1
For patients experiencing severe gastrointestinal symptoms on tirzepatide, monitor electrolytes vigilantly (potassium, magnesium, calcium) to prevent arrhythmias from electrolyte depletion 4. This is particularly important at higher doses (15 mg weekly) or in patients with additional risk factors 4.