Tirzepatide Linked to Ketoacidosis in Non-Diabetic Patient

Tirzepatide, a dual GLP-1/GIP receptor agonist, is widely used for managing type 2 diabetes and obesity, known for its potent glucose-lowering and weight-reducing effects. While diabetic ketoacidosis (DKA) is a known, albeit rare, complication in diabetic patients, its occurrence in individuals without diabetes is highly unusual. This case report addresses the unexpected development of ketoacidosis and hyperglycemia in a patient without a prior diagnosis of diabetes while on Tirzepatide.

The patient presented with severe nausea, vomiting, and abdominal pain, indicative of a metabolic crisis. Laboratory analysis revealed profound hyperglycemia with a blood glucose level of 485 mg/dL, a significantly reduced serum bicarbonate of 10 mEq/L, and an arterial pH of 7.15, confirming severe metabolic acidosis. Furthermore, urine ketone levels were +++ and serum beta-hydroxybutyrate was markedly elevated at 7.2 mmol/L (normal range <0.6 mmol/L), unequivocally diagnosing ketoacidosis. > The most critical finding was the acute onset of severe ketoacidosis and hyperglycemia in a patient with no prior history of diabetes mellitus following Tirzepatide initiation. After immediate discontinuation of Tirzepatide and aggressive treatment with intravenous fluids and insulin, the patient's blood glucose normalized to 120 mg/dL within 24 hours, and her ketone levels resolved within 48 hours, demonstrating a clear temporal relationship between the drug and the adverse event. This rapid resolution after drug cessation strongly suggests Tirzepatide as the precipitating factor.