MON-730 - An Uncommon Complication of A Common Therapy: Starvation Ketoacidosis Associated with Tirzepatide

Introduction:
Starvation ketoacidosis is an uncommon but potentially serious complication resulting from prolonged caloric deficiency and may present as euglycemic ketoacidosis. Gastrointestinal adverse effects are well recognized with glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists; however, starvation ketoacidosis has been rarely reported.

Case Presentation:
We report a young female who presented with severe starvation ketoacidosis following re-initiation of tirzepatide. She had a baseline body mass index (BMI) of 31 kg/m², which decreased to 22 kg/m² after one year of tirzepatide therapy which she initiated herself without supervision by a physician. She was maintained on a maximum dose of 5 mg weekly due to gastrointestinal intolerance and discontinued the medication herself for three weeks. She restarted trizepatide at 2.5 mg weekly, and one day after injection she developed severe nausea and recurrent vomiting (approximately 11 episodes in one day), prompting emergency department presentation.
Laboratory evaluation revealed high anion gap metabolic acidosis with pH 7.18, bicarbonate 10.5 mmol/L, sodium 133 mmol/L, chloride 99 mmol/L, anion gap 23.5, and urine ketones 3+. Blood glucose was normal at 4.47 mmol/L, with no evidence of hyperglycemia. Other causes of high anion gap metabolic acidosis were excluded based on history and laboratory findings. Clinically, the patient was tachycardic (heart rate 116 beats per minute), normotensive, and dehydrated, with no evidence of infection or use of other new medications.

Management and Outcome:
The patient was treated with intravenous fluids, including 5% dextrose in 0.45% saline. This resulted in significant improvement in metabolic parameters, with pH rising to 7.33, bicarbonate to 19 mmol/L, and anion gap decreasing to 11. Clinical signs of dehydration resolved, and tachycardia improved.

Conclusion:
This case highlights a rare presentation of starvation ketoacidosis following re-initiation of GLP-1/GIP receptor agonist therapy in the absence of hyperglycemia. With the increasing use of these agents, starvation ketoacidosis should be considered in patients presenting with gastrointestinal intolerance and metabolic acidosis. Early recognition, appropriate management, and patient education regarding potential adverse effects are essential. Close monitoring, medical supervision and prompt evaluation are warranted to prevent serious complications.

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