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 to manage type 2 diabetes mellitus (T2DM) because of 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. The risk of this interaction may be increased with the concurrent use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly during periods of reduced caloric intake or the presence of 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 practiced prolonged intermittent fasting. One week prior, she had started metformin and enavogliflozin, a selective SGLT2 inhibitor. Laboratory results showed a glucose level of 137 mg/dL, urine ketones (+++), lactate level of 4.87 mg/dL, HbA1c of 9.3%, C-peptide of 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 a stable condition. Conclusion: This case highlights the importance of recognizing euDKA in patients using SGLT2 inhibitors and GLP-1RAs, particularly those with fasting or gastrointestinal symptoms. Clinicians should suspect euDKA even without significant hyperglycemia to enable prompt diagnosis and management, thereby preventing complications.