SGLT2 Inhibitor and Euglycemic DKA in Type 2 Diabetes
A 58-year-old man with type 2 diabetes (T2D) for 10 years, BMI 32 kg/m², HbA1c 8.4%, eGFR 55 mL/min/1.73 m², and albuminuria (UACR 350 mg/g). He has hypertension and heart failure with reduced ejection fraction (HFrEF, EF 35%). His current medications: metformin 1000 mg BID, empagliflozin 10 mg daily, sacubitril/valsartan, carvedilol, spironolactone, and atorvastatin. He presents to the emergency department with 2 days of nausea, vomiting, and abdominal pain. He reports a recent upper respiratory infection and decreased oral intake. Labs: glucose 210 mg/dL, arterial pH 7.25, bicarbonate 14 mEq/L, anion gap 22, beta-hydroxybutyrate 4.5 mmol/L, creatinine 1.4 mg/dL (baseline 1.2). He is diagnosed with euglycemic diabetic ketoacidosis (DKA).
1. Explain the pathophysiology of euglycemic DKA associated with SGLT2 inhibitors and identify the precipitating factors in this case.
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SGLT2 inhibitors promote glycosuria, lowering glucose levels, but also increase glucagon secretion and ketone production. The combination of reduced carbohydrate availability (due to illness and decreased intake), increased counterregulatory hormones (from infection), and SGLT2 inhibitor effect leads to ketosis. Because glucose is being excreted, glucose levels may not be markedly elevated (<250 mg/dL), hence 'euglycemic.' Precipitants here: acute illness (URI) causing stress hormone release, decreased oral intake leading to starvation ketosis, and possibly dehydration. His reduced eGFR may also contribute to drug accumulation. The diagnosis requires high index of suspicion; measurement of beta-hydroxybutyrate is key.
2. Outline the acute management of euglycemic DKA in this patient, including fluid, insulin, and electrolyte strategies, and discuss whether the SGLT2 inhibitor should be continued long-term.
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Management: (1) Hold SGLT2 inhibitor immediately. (2) Aggressive IV fluid resuscitation with isotonic saline to restore volume, then switch to dextrose-containing fluids (e.g., D5 1/2NS) when glucose <250 mg/dL to allow continued insulin administration without hypoglycemia. (3) IV insulin infusion (0.1 units/kg/hr) to suppress ketogenesis; continue until anion gap closes and ketones clear. (4) Monitor and replace electrolytes: potassium (may be low despite normal serum due to total body depletion), magnesium, phosphate. (5) Treat precipitating illness. (6) Monitor glucose hourly, electrolytes every 2–4 hours, and beta-hydroxybutyrate. Long-term: SGLT2 inhibitors have cardiovascular and renal benefits, especially in HFrEF and CKD with albuminuria. After resolution and education on sick-day management, the SGLT2 inhibitor can be restarted once the patient is stable and eating, with clear instructions to hold during acute illness, prolonged fasting, or surgery (e.g., 3–4 days before). Consider alternative if recurrent DKA. Emphasize sick-day rules: hold SGLT2i, maintain hydration, check ketones if symptoms.