# Beyond Glycemia: Pharmacology-Driven Ketogenesis and Euglycemic DKA with SGLT2 Inhibitors—A Practical Review for Acute Care

## TL;DR

This review explains how SGLT2 inhibitors can cause a rare but dangerous condition called euglycemic diabetic ketoacidosis and provides guidance for its diagnosis and treatment.

## Contribution

The paper offers a practical, pharmacology-focused review of euglycemic DKA mechanisms and acute care management strategies.

## Key findings

- SGLT2 inhibitors can cause euglycemic DKA, which is often missed due to normal blood glucose levels.
- Management includes volume resuscitation, ketone testing, insulin with dextrose, and electrolyte replacement.
- Prevention involves 'sick-day' rules and withholding SGLT2 inhibitors during illness or surgery.

## Abstract

Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are widely prescribed for type 2 diabetes, heart failure, and chronic kidney disease. A rare but dangerous adverse event is SGLT2i-associated diabetic ketoacidosis, often euglycaemic (euDKA), and therefore easy to miss. This narrative review summarizes mechanisms, triggers (fasting, dehydration, infection, perioperative stress), and ketone-centred pathways for diagnosis, treatment, and prevention in acute-care settings. Management priorities are volume resuscitation, blood β-hydroxybutyrate and acid–base testing, insulin infusion with dextrose to suppress ketogenesis, and electrolyte replacement. Prevention relies on “sick-day” rules, perioperative drug withholding, and a low threshold for ketone testing in any patient with high-anion-gap acidosis, despite normal or mildly elevated glucose.