Case Presentation: A 53-year-old man with a history of insulin-dependent type 2 diabetes mellitus presented with the complaint of abdominal pain, emesis and poor oral intake for three days. CT scan revealed non-obstructing nephrolithiasis. He was started on continuous IV fluids and pain management. Initial urinalysis revealed glucosuria >1000 mg/dL and negative ketones. Home medications including metformin, empagliflozin and insulin were continued on admission. On day three of hospitalization he developed acute encephalopathy initially attributed to opioid overdose, but persisted despite naloxone administration. Repeat urinalysis revealed interval development of ketonuria >80mg/dL. He was transferred to our tertiary care center for further management.
On arrival, patient was somnolent and oriented to self only. The remainder of his physical exam was unremarkable. Labs revealed blood glucose of 135 mg/dL, high anion gap metabolic acidosis and beta-hydroxybutyrate of 5.74 mmol/L. Expanded drug screen and ingestion panels were negative. Encephalopathy and metabolic derangements resolved with supportive care. On further review of home medications, his SGLT2 inhibitor was determined to be the cause of his euglycemic ketoacidosis (euDKA) in the setting of nephrolithiasis. He was discharged on basal and bolus insulin and metformin. Empagliflozin was discontinued.
Discussion: The mechanism of action of SGLT2 inhibitors involves selectively inhibiting glucose reuptake in the proximal tubules of the kidneys resulting in reduction of blood glucose levels through glucosuria. The low-glucose state caused by SGLT2 inhibitors leads to increased lipolysis, gluconeogenesis, and a mild ketogenic state. This is exacerbated by the combination of SGLT2 inhibitors and a state of starvation ketosis or reduced oral intake. The diagnosis of euDKA is often delayed due to normal blood glucose levels induced by SGLT2 inhibitors. Standard of care includes initiation of an insulin drip and fluid resuscitation until the anion gap has closed. Case reports reveal euDKA secondary to empagliflozin is often associated with an acute infection and/or inflammatory state (pancreatitis, gastroenteritis, influenza, and cholecystitis) inducing poor oral intake and starvation ketosis. Similar to these cases, our patient had poor oral intake due to nausea and emesis secondary to nephrolithiasis. Despite the similarities, our case is unique in that the patient developed ketoacidosis after admission caused by continuation of his SGLT2 inhibitor upon admission. EuDKA could have been avoided if his SGLT2 had been held on admission.
Conclusions: Euglycemic ketoacidosis is a rare but serious side effect of SGLT2 inhibitors. Multiple triggers can precipitate euDKA induced by SGLT2 inhibitors including poor oral intake, infectious states, and relative insulin deficiency. Hospitalists should be aware of the risks associated with continuing SGLT2 inhibitors with poor oral intake and must consider discontinuing these medications during acute hospitalization.