A Novel Presentation of Euglycemic Diabetic Ketoacidosis Associated with SGLT2 Inhibitor and Weekly GLP-1 Agonist: Case report

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are widely used in managing type 2 diabetes mellitus (T2DM) due to their glucose-lowering and cardioprotective effects. However, euglycemic diabetic ketoacidosis (euDKA) is an uncommon but serious adverse event. EuDKA is characterized by metabolic acidosis and ketosis with only mild to moderate hyperglycemia, making diagnosis challenging. Risk may be elevated with concurrent use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), especially during reduced caloric intake or gastrointestinal symptoms. Case: A 38-year-old woman with newly diagnosed T2DM presented with five days of fatigue, poor oral intake, nausea, and vomiting. She had recently initiated semaglutide (GLP-1RA) for weight loss and was practicing prolonged intermittent fasting. One week prior, she was started on metformin and enavogliflozin, a selective SGLT2 inhibitor. Laboratory results showed glucose 137 mg/dL, urine ketones (+++), lactate 4.87 mg/dL, HbA1c 9.3%, C-peptide 0.88 ng/mL, and high anion gap metabolic acidosis. She was diagnosed with euDKA and treated with IV fluids, insulin infusion, dextrose, and potassium supplementation. Her symptoms resolved, and she was discharged in stable condition. Conclusion: This case emphasizes the importance of recognizing euDKA in patients using SGLT2 inhibitors and GLP-1RAs, particularly with fasting or gastrointestinal symptoms. Clinicians should suspect euDKA even without significant hyperglycemia, enabling prompt diagnosis and appropriate management to prevent complications.