Tirzepatide Linked to Ketoacidosis in Non-Diabetic, Non-Obese Individual

Euglycemic ketoacidosis (EKA) is a serious metabolic condition characterized by high levels of ketone bodies and metabolic acidosis despite normal or mildly elevated blood glucose, often associated with SGLT2 inhibitors, prolonged fasting, or acute illness. While tirzepatide is a powerful dual GLP-1/GIP receptor agonist used for type 2 diabetes and obesity, its potential to induce EKA, particularly in individuals without pre-existing diabetes or obesity, is not well-established, leaving a critical gap in understanding its full safety profile and risk factors. This case report aims to address this by documenting such an occurrence.

The patient, a nonobese individual without diabetes, developed euglycemic ketoacidosis following the initiation of tirzepatide therapy. Laboratory tests revealed significantly elevated serum ketone bodies, with beta-hydroxybutyrate levels peaking at 5.2 mmol/L, alongside a pronounced high anion gap metabolic acidosis, indicated by an anion gap of 22 mEq/L. Crucially, plasma glucose levels remained consistently below 250 mg/dL, typically ranging between 110 mg/dL and 180 mg/dL, confirming the euglycemic nature of the ketoacidosis. The most critical finding was the clear temporal association between tirzepatide use and the onset of euglycemic ketoacidosis in a patient devoid of conventional risk factors like diabetes or obesity. Upon discontinuation of tirzepatide and initiation of appropriate supportive medical management, the patient's metabolic derangements rapidly improved, with ketone levels normalizing within 48 hours and the acidosis resolving completely within 72 hours.