Life-Threatening Ventricular Fibrillation Linked to High-Dose Tirzepatide-Induced Gastrointestinal Side Effects

Tirzepatide is a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, used for the treatment of type 2 diabetes and obesity, and recently approved for obstructive sleep apnea. It is known to cause gastrointestinal (GI) side effects; however, these are generally not severe enough to be life-threatening. We present a unique case of a 57-year-old woman with no prior cardiac history who was on a high dose of tirzepatide (15 mg weekly) for weight loss. After her dose was increased to 15 mg, she developed severe GI symptoms, including prolonged vomiting and diarrhea, leading to profound electrolyte imbalances (K⁺ 2.2, Mg²⁺ 1.1, and corrected Ca²⁺ 5.6) and ultimately resulting in ventricular fibrillation and cardiac arrest. The patient was successfully resuscitated and stabilized with electrolyte correction. A comprehensive evaluation, including left heart catheterization, ruled out obstructive coronary artery disease. Following the cardiac arrest, the patient had severely reduced left ventricular function, likely due to hypoxia and post-cardiac arrest stunning. However, her ejection fraction significantly improved within a few weeks, suggesting that tirzepatide-associated GI side effects and subsequent electrolyte disturbances were the primary precipitating factors. This case highlights a previously undocumented risk of life-threatening arrhythmias due to severe electrolyte disturbances caused by tirzepatide-induced GI side effects. Vigilant electrolyte monitoring is crucial, particularly in patients on high doses or those with additional risk factors.