Case Report: Diabetic ketoacidosis after co-administration of empagliflozin and probenecid

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are filtered and secreted to their primary site of action in the proximal tubule of the kidney. Many commonly used medications have potential to diminish renal elimination of SGLT2 inhibitors by inhibiting their tubular secretion. We present a case of severe diabetic ketoacidosis (DKA) in a patient with type 2 diabetes occurring several days after co-prescription of empagliflozin and probenecid. Other than the recent introduction of empagliflozin, no cause for the DKA episode was apparent. A pharmacokinetic interaction between probenecid and empagliflozin, involving organic anion transporter 3 (OAT3), reduces proximal tubular secretion of empagliflozin. Co-administration of an OAT3 inhibitor, such as probenecid, with empagliflozin may increase patient exposure and diminish glucosuric response to the SGLT2 inhibitor, thereby increasing the risk of DKA. We suggest that clinicians exercise caution when prescribing empagliflozin alongside inhibitors of OAT3 in patients with type 2 diabetes.