Unsupervised Tirzepatide Use Induces Severe Euglycemic Ketoacidosis in Non-Obese, Non-Diabetic Woman

While Tirzepatide, a dual GLP-1R and GIPR agonist, is approved for type 2 diabetes and chronic weight management, its off-label use in individuals without these conditions is rising. A known side effect is appetite suppression and gastrointestinal intolerance, which can lead to significant caloric reduction. This report highlights a rare but serious complication: euglycemic ketoacidosis (EKA), typically associated with SGLT-2 inhibitors, now observed in a non-diabetic, non-obese individual using Tirzepatide, underscoring a critical safety gap.

This case report details a 30-year-old woman with a BMI of 24.8 kg/m² and no history of diabetes who presented with 4 days of severe nausea, approximately 10 vomiting episodes daily, poor intake, and abdominal pain. She had self-administered Tirzepatide 2.5 mg once weekly, increasing the dose to 5 mg once weekly 1 week prior to presentation. Initial assessment included blood gas analysis, electrolyte panel, lactate, urine ketones, and serum ketones to diagnose metabolic derangements and determine the primary endpoint of acidosis resolution.

Upon presentation, the patient exhibited severe high anion gap metabolic acidosis with a pH of 7.15, a bicarbonate level of 10.5 mEq/L, and an anion gap of 24. Her lactate level was within the normal range, while urine ketones were positive and serum ketones measured 4.5 mmol/L. Crucially, her glucose level was 4.2 mmol/L, confirming euglycemia. Acidosis persisted despite initial administration of 1.5 L crystalloid. Tirzepatide was discontinued, and she received supportive care including 10% dextrose, lactated Ringer's solution, thiamine, antiemetics, and electrolyte management.

The anion gap closed and ketones normalized within 36 hours without the need for bicarbonate therapy or insulin infusion, indicating a rapid reversal with caloric support and cessation of the drug.