Ketoacidosis associated with tirzepatide use in a nonobese individual without diabetes

Abstract Euglycemic ketoacidosis is metabolic acidosis with elevated ketone bodies despite normal or mildly elevated glucose levels and has rarely been reported in nonobese individuals without diabetes using tirzepatide. A 23-year-old Japanese woman without obesity presented with a 4-day history of nausea, vomiting, and diarrhea after the second self-administered dose of tirzepatide (2.5 mg) obtained through an aesthetic clinic without ongoing medical supervision. She had no history of diabetes, alcohol consumption, or carbohydrate restriction. Laboratory results showed high anion gap metabolic acidosis (anion gap: 25.9 mmol/L) normal reference range (ref): 8-16 mmol/L, elevated serum β-hydroxybutyrate (5.5 mmol/L) (ref: 0.07 mmol/L) and acetoacetate (1.4 mmol/L) (ref: 0.01-0.07 mmol/L), with concomitant metabolic alkalosis compatible with vomiting and mild hyperglycemia (196 mg/dL SI:10.9 mmol/L) (ref: 70-100 mg/dL SI: 3.9-5.6 mmol/L). No definitive infectious source was identified on evaluation, and euglycemic ketoacidosis was diagnosed. She received intravenous fluids containing glucose, electrolytes, and continuous insulin infusion, which rapidly corrected the acidosis. Her symptoms resolved within several days, and follow-up evaluation confirmed normal glucose tolerance. This case adds to the limited clinical evidence of tirzepatide-associated euglycemic ketoacidosis in a non-obese individual without diabetes. Caution is warranted regarding the off-label use of tirzepatide for aesthetic weight reduction.