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Beyond Glycemia: Pharmacology-Driven Ketogenesis and Euglycemic DKA with SGLT2 Inhibitors-A Practical Review for
Massimo Meco1, Emiliano Agosteo1, Pierluigi Zulli2
1Department of Anaesthesia and Intensive Care, San Carlo Clinic, 20037 Paderno Dugnano, Italy.
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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