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.

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.

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