BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes and chronic weight management in adults meeting clinical criteria. Appetite suppression and gastrointestinal intolerance can markedly reduce intake. This report describes a 30-year-old woman with tirzepatide-associated euglycemic ketoacidosis after unsupervised use of tirzepatide obtained without a prescription for weight loss, despite having no history of obesity or diabetes.

CASE REPORT: A 30-year-old woman with a body mass index of 24.8 kg/m² and no known diabetes presented with 4 days of severe nausea, approximately 10 vomiting episodes daily, poor intake, and periumbilical abdominal pain. She had self-administered tirzepatide 2.5 mg once weekly and increased the dose to 5 mg 1 week before presentation. Initial testing showed high anion gap metabolic acidosis with a pH of 7.15, bicarbonate level of 10.5 mEq/L, and an anion gap of 24. Lactate was in the normal range. Urine ketones were positive, serum ketones measured 4.5 mmol/L, and glucose level was 4.2 mmol/L. Acidosis persisted after administration of 1.5 L crystalloid, prompting intensive care unit admission. Tirzepatide was stopped. She received 10% dextrose, lactated Ringer’s solution, thiamine, antiemetics, electrolyte monitoring and replacement, and gradual refeeding. The anion gap closed and ketones normalized within 36 hours, without bicarbonate therapy or insulin infusion.

CONCLUSIONS: Tirzepatide-related nausea, vomiting, and caloric deprivation can be associated with significant euglycemic ketoacidosis even without diabetes or obesity. Clinicians should consider starvation ketoacidosis in tirzepatide users with vomiting, poor intake, abdominal pain, and high anion gap metabolic acidosis.

Keywords: Case Reports, Endocrinology, ketoacidosis, Tirzepatide