(985) Significantly Delayed Onset of Euglycemic Diabetes Ketoacidosis With SGLT2i Therapy: A Case Report

Introduction: Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a mainstay of diabetes treatment. Improved hemoglobin A1C, weight loss, and protection against cardiovascular events are a few of their benefits. Use of SGLT2i increases as evidence of cardioprotective effects are published, specifically reduced hospitalizations for heart failure and decreased mortality. Reports of euglycemic diabetic ketoacidosis (EuDKA) with SGLT2i also increase. Prompt diagnosis of EuDKA is problematic, and 50% of patients experience a delay in diagnosis due to lack of recognition. Risk factors for EuDKA from SGLT2i include infection, surgery, fasting, alcohol intake, trauma, or an acute vascular event. SGLT2i therapy should stop at least 3 days prior to a surgery in order to prevent EuDKA.

Description: We present the case report of a patient on empagliflozin who developed EuDKA after emergent surgery. Seven days after empaglifozin was stopped and 6 days after emergent vertebrae fusion and decompression, the patient presented to intensive care with metabolic acidosis (pH < 7.15; bicarbonate = 6 mmol/L), positive anion gap (27 mmol/L) and normal lactic acid (0.8 mmol/L). The patient's renal function was normal (CrCl > 50mL/min) but required emergent hemodialysis for acid clearance. The patient's glucoses were < 180 mg/dL. EuDKA was not identified for another 24 hours, when beta-hydroxybutyrate resulted > 4.5mmol/L. Intravenous insulin was immediately initiated. After 24 hours of IV insulin, bicarbonate improved to 25 mmol/L and anion gap was 12 mmol/L. The patient recovered fully. Empagliflozin was not continued.

Discussion: Physiologic stress from surgery, a known risk factor for EuDKA, increases adrenaline, cortisol, and glucagon, which all increase insulin resistance. SGLT2i mechanism of action causes ketogensis, lipolysis, and glucosuria. EuDKA typically occurs within 48-72 hours after the last dose of SGLT2i and a surgery. However, we report a case of EuDKA more than 168 hours after the last dose of empagliflozin and 144 hours after surgery. The half life of empaglifozin is 12 hours, indicating full clearance occurs by 60 hours. Investigation into delayed onset EuDKA in patients on SGLT2i agents requires further investigation, and patients on SGLT2i agents must be evaluated early for EuDKA.