Euglycemic Ketoacidosis Following Coadministration of an SGLT2 Inhibitor and Tirzepatide

Euglycemic ketoacidosis (EKA) is a life-threatening condition characterized by ketone production leading to systemic acidosis, dehydration, and end-organ damage. It presents similarly to diabetic ketoacidosis, except that patients have normal to slightly elevated blood glucose levels. EKA is an increasingly recognized complication of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. Recently the novel dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist tirzepatide was approved for treatment of diabetes and weight loss. Here, we describe a unique case in which a patient placed on both an SGLT2 inhibitor and tirzepatide to treat type 2 diabetes was admitted to the intensive care unit (ICU) for EKA. To our knowledge, this is the first case detailing a patient developing this serious condition after starting tirzepatide for diabetes. The patient required treatment and monitoring in an ICU to make a full recovery. As tirzepatide is a relatively new medication whose side effect profile has yet to be fully characterized, clinicians should be aware of this rare yet potentially fatal complication.