Euglycemic Diabetic Ketoacidosis in Patients on Sodium–Glucose Cotransporter-2 Inhibitors: A Preliminary Observation from Eastern India

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a transformative class of antidiabetic agents known for their cardiometabolic benefits.However, they have been increasingly implicated in an uncommon but serious complication-euglycemic diabetic ketoacidosis (EDKA)-characterized by ketoacidosis in the absence of significant hyperglycemia.Timely recognition is often delayed due to its subtle clinical and biochemical profile.Objective: To analyze the clinical characteristics, precipitating factors, laboratory findings, management strategies, and outcomes of patients with SGLT2i-associated EDKA from tertiary care centers in Eastern India. Materials and methods:A retrospective multicenter observational study was conducted across five tertiary care hospitals in Kolkata over a 5-year period.Adult patients (>18 years) with type 2 diabetes mellitus (T2DM) on SGLT2i who presented with diabetic ketoacidosis (DKA) were screened.Euglycemic diabetic ketoacidosis was diagnosed based on blood glucose <250 mg/dL, arterial pH 7.3, serum bicarbonate 18 mEq/L, or anion gap >10, and positive serum or urine ketones.Data were collected on demographics, clinical presentation, biochemical parameters, and treatment outcomes.Results: Among the 5,642 DKA cases in patients on SGLT2i, 10 cases (0.18%) were identified as EDKA.The median age was 62 years, and common presenting symptoms included nausea, vomiting, fatigue, and abdominal discomfort.Dapagliflozin and empagliflozin were the most commonly implicated agents.Identified triggers included infections (respiratory, urinary, and COVID-19), perioperative stress, and acute pancreatitis.Despite normal or modestly elevated glucose levels (range: 144-226 mg/dL), patients exhibited significant metabolic acidosis (mean pH: 7.23; mean anion gap: 24).All patients were managed in the intensive care unit with fluid resuscitation, insulin infusion, electrolyte correction, and early carbohydrate supplementation using a structured surgical trial in traumatic intracerebral hemorrhage (STITCH) protocol.Nine patients recovered uneventfully; one succumbed to COVID-19-related complications.Conclusion: Euglycemic diabetic ketoacidosis, although rare, is a potentially life-threatening complication of SGLT2i therapy.High clinical vigilance is warranted, especially in the context of concurrent infections or surgical stress.Early identification, protocol-based management, and patient education are essential to improving outcomes.