BACKGROUND: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, is increasingly used for obesity treatment, including in individuals without diabetes. Starvation ketoacidosis is a rare but serious complication associated with reduced caloric intake and enhanced ketogenesis. Reports of tirzepatide-associated starvation ketoacidosis in non-diabetic patients remain limited, and none have been reported in East Asian populations.
CASE PRESENTATION: A 21-year-old Japanese woman with obesity initiated weekly subcutaneous tirzepatide (2.5 mg/week) for weight loss while practicing carbohydrate restriction. After the fifth injection, she developed persistent nausea and vomiting, leading to markedly reduced oral intake. She presented to the emergency department with hypoglycemia (68 mg/dL) and severe high-anion gap metabolic acidosis (pH 7.22, bicarbonate 10 mmol/L, anion gap 22.6 mmol/L). Urinalysis revealed ketonuria, and serum ketone levels were markedly elevated. She had lost 21 kg one month after the initiation of tirzepatide. No infection, toxin exposure, or alternative metabolic disorder was identified. Starvation ketoacidosis was diagnosed. Treatment with intravenous glucose-containing fluids resulted in rapid resolution of metabolic acidosis within 12 h without insulin therapy.
CONCLUSIONS: This case demonstrates that tirzepatide can precipitate starvation ketoacidosis in non-diabetic individuals, particularly when gastrointestinal adverse effects or dietary restriction lead to caloric deprivation. As the first reported case in an East Asian patient, it highlights the need for emergency physicians to consider starvation ketoacidosis in patients using tirzepatide for weight loss who present with vomiting, poor intake, or rapid weight loss. Early recognition and appropriate metabolic assessment are essential, and in patients with preserved endogenous insulin secretion, prompt glucose administration may allow rapid recovery without need for insulin therapy.
