Journal of Personalized Medicine · Mar 10, 2026

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

By Meco M, Agosteo E, Zulli P et al.

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.

doi.org/10.3390/jpm16030156Open accessPubMed 41893024Interventions