SUN-627 - Euglycemic Ketoacidosis Following Initiation of Tirzepatide in A Nondiabetic Patient

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for weight management and glycemic control because of their favorable metabolic and cardiovascular profiles. While gastrointestinal adverse effects are common, euglycemic diabetic ketoacidosis (euDKA) remains a rare and underrecognized complication. We report a case of euDKA occurring shortly after initiation of tirzepatide in a patient without diabetes.
A 43-year-old woman with no history of diabetes, obesity-related metabolic syndrome, hypertension and hyperthyroidism presented to the emergency department with one day of nausea, vomiting, and worsening left-sided abdominal pain. She reported receiving her first dose of tirzepatide (2.5 mg) the day prior to symptom onset. She denied any additional symptoms of fevers,chills, chest pain, syncope or any loss of consciousness.
Initial laboratory evaluation revealed leukocytosis (WBC 16.5 × 10⁹/L), hemoglobin 15.7 g/dL, and platelets 455 × 10⁹/L. ABG was drawn showing a mixed acid–base disturbance with a pH of 7.62, pCO₂ < 15 mmHg, and bicarbonate of 13 mmol/L. Complete Metabolic panel showed elevated anion gap of 20, sodium 148 mmol/L, potassium 3.6 mmol/L, creatinine 1.0 mg/dL , phosphorus 2.4 mg/dL, and mildly elevated lactate at 2.1 mmol/L. Serum glucose was 141. Serum beta hydroxybutyrate was elevated at 1.10 mmol/L.Urinalysis was positive for ketones with negative glucose. Triglycerides were 77 mg/dL, and thyroid-stimulating hormone was 1.89 µIU/mL.CT of abdomen and pelvis revealed scattered colonic diverticula without evidence of diverticulitis, post-cholecystectomy changes, mild biliary ductal dilation (common bile duct measuring 14 mm) without choledocholithiasis, and a normal-appearing pancreas.Over the next 24 hours, her anion gap closed and repeat arterial blood gas demonstrated improvement after which the insulin infusion was discontinued, and she was transitioned to oral intake.HgbA1C was 5.2% confirming non diabetic diagnosis.The patient remained clinically stable and was discharged with endocrinology follow-up and strict instructions to avoid further use of GLP-1 receptor agonists.
Euglycemic diabetic ketoacidosis is characterized by ketosis and metabolic acidosis in the absence of significant hyperglycemia and is most commonly associated with SGLT2 inhibitors. GLP-1 RA–associated euDKA is a rare but serious side effect.
Clinicians should maintain a high index of suspicion for euglycemic ketoacidosis in patients presenting with unexplained anion gap metabolic acidosis and ketosis following initiation of GLP-1 receptor agonists, even in the absence of diabetes. Early recognition and prompt treatment are critical to prevent morbidity.

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