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

## TL;DR

A patient with type 2 diabetes developed severe diabetic ketoacidosis after taking empagliflozin and probenecid together, likely due to a drug interaction.

## Contribution

The paper identifies a pharmacokinetic interaction between empagliflozin and probenecid via OAT3 that increases DKA risk.

## Key findings

- Co-administration of empagliflozin and probenecid may reduce empagliflozin secretion in the kidney.
- This interaction could increase empagliflozin exposure and raise the risk of diabetic ketoacidosis.
- Clinicians should be cautious when prescribing OAT3 inhibitors with empagliflozin.

## 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.