SGLT2 Inhibitor–Induced Euglycemic Diabetic Ketoacidosis: A Case Report

Euglycemic diabetic ketoacidosis is a rare but serious adverse effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We present a case of a woman in her 40s with type 2 diabetes mellitus hospitalized for revascularization for moyamoya disease who developed empagliflozin-associated euglycemic diabetic ketoacidosis despite having stopped the medication before admission. Surgical stress, acute postoperative illness, and decreased carbohydrate intake are postulated to be contributing factors to the development of ketosis in this patient, while near-normal glucose levels initially suggested nondiabetic ketoacidosis physiology and led to delayed diagnosis and treatment. Patients with type 2 diabetes mellitus may develop diabetic ketoacidosis during states of relative insulinopenia, most frequently from inadequate medication or intercurrent illness. During periods of carbohydrate deficiency, volume depletion, and upregulation of counter-regulatory stress hormones, SGLT2 inhibitor therapy can promote lipolysis and ketogenesis while maintaining euglycemia. Clinical considerations to ensure safe SGLT2 inhibitor therapy include appropriate holding parameters, timely diagnosis of euglycemic diabetic ketoacidosis, and recognition that the pharmacologic effects of SGLT2 inhibitor treatment may persist beyond several half-lives of elimination.