SGLT2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis (EDKA) in Hematologic Malignancy Patients: A Case Series

Sodium-glucose Cotransporter 2 inhibitors (SGLT2i) are widely used and effective pharmacotherapeutic options that are first-line therapy for Type 2 diabetes mellitus (T2DM) and congestive heart failure. A major adverse effect of SGLT2i usage is diabetic ketoacidosis (DKA). SGLT2i-induced DKA commonly presents as euglycemic DKA (EDKA). The safety of empagliflozin in cancer patients is not well established. High intensity treatment of hematologic malignancy poses a unique set of risk factors for EDKA. Four cases of empagliflozin-associated EDKA in hematologic malignancy patients were identified through pharmacy adverse event reporting at a cancer research hospital. All patients were euglycemic except one patient who required CRS/ICANS treatment with dexamethasone, causing steroid-induced hyperglycemia. All four patients had weight loss due to reasons including, but not limited to, reduced oral intake, diarrhea, nausea, and pain. Infections and/or neutropenic fever were also commonalities throughout the four patients. In all patients, DKA contributed to iatrogenic ICU admissions and prolonged hospital stays. SGLT2i use in hematologic malignancy patients may increase the risk of DKA due to high risk of anorexia, weight loss, and infections, all highly associated with intensive treatment that can disrupt the availability and sensitivity to insulin. In patients receiving SGLT2i, clinicians should be aware of risk factors for DKA as well as potential euglycemic presentation to ensure close clinical and laboratory monitoring to facilitate rapid diagnosis and treatment of DKA.