SUN-654 - Euglycemic Diabetic Ketoacidosis during GLP-1 Receptor Agonist Up-Titration in A Patient with Lower Body Mass Index on SGLT2 Inhibitor Therapy

Background
Sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) receptor agonists are commonly prescribed together in patients with type 2 diabetes (T2DM) due to benefits in glycemic control, cardiovascular risk reduction, and weight loss. Euglycemic diabetic ketoacidosis (euDKA) is a rare but serious complication of SGLT2 inhibitor therapy and may be overlooked as glucose levels are often normal or only mildly elevated. GLP-1 receptor agonists frequently cause gastrointestinal side effects such as nausea, vomiting, and reduced oral intake, particularly during dose escalation. In patients with lower body mass index (BMI), reduced intake while on an SGLT2 inhibitor may increase the risk of ketosis and euDKA.
Case
A 57-year-old woman with T2DM, hypertension, and hyperlipidemia presented with one day of epigastric pain, intractable nausea and vomiting, and syncope. Her medications included empagliflozin and oral semaglutide, which had been initiated three months earlier with dose escalation approximately six weeks prior. She had a BMI of 18.6 kg/m² and reported unintentional 30-pound weight loss over one year, with no history of being overweight. Her hemoglobin A1c at presentation was 16.1%. Labs demonstrated serum glucose of 241 mg/dL, an anion gap metabolic acidosis (anion gap 21.1), elevated beta-hydroxybutyrate of 7.33 mmol/L, and serum lactate of 1.60 mmol/L. She was treated with intravenous fluids, electrolyte repletion, and insulin therapy for euDKA, with resolution of acidosis.
Conclusion
This case highlights important risk factors for euglycemic diabetic ketoacidosis in patients treated with combined GLP-1 receptor agonist and SGLT2 inhibitor therapy. In this patient, euDKA developed shortly after GLP-1 dose escalation, suggesting this may be a higher-risk period. Patients with lower body mass index may have less metabolic reserve and may be more vulnerable when GLP-1–related gastrointestinal side effects lead to reduced oral intake. Clinicians may consider temporarily holding SGLT2 inhibitors during GLP-1 dose escalation or during periods of poor oral intake, particularly in patients with lower BMI or significant recent weight loss. Early ketone testing in symptomatic patients may help prevent delayed diagnosis and severe metabolic acidosis.

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