A 49-year-old man with T2DM on metformin and empagliflozin (Jardiance) 25 mg daily presents to urgent care with 2 days of nausea, vomiting, diffuse abdominal pain, and malaise. He has eaten little for 48 hours. On exam he is tachypneic with fruity breath. Labs: pH 7.22, anion gap 22, serum bicarbonate 12 mEq/L, beta-hydroxybutyrate 5.8 mmol/L, serum glucose 192 mg/dL, lactate 1.8, urine ketones large. Which of the following is the most likely diagnosis?

Question

Accepted Answer

✅ D. Euglycemic diabetic ketoacidosis secondary to SGLT2 inhibitor use

SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) classically cause euglycemic DKA — ketoacidosis with a serum glucose typically <250 mg/dL, often in the 150–200 range. The mechanism involves increased glucagon secretion, decreased insulin, and continuous urinary glucose loss that masks hyperglycemia while ketogenesis proceeds. Triggers include fasting, surgery, infection, low-carb diets, and alcohol. Diagnosis requires a high index of suspicion: any SGLT2-treated patient with anion-gap acidosis and ketones should be worked up for DKA even with normal glucose.

❌ A. Gastroenteritis with dehydration
While nausea/vomiting and abdominal pain are present, the anion gap metabolic acidosis with markedly elevated beta-hydroxybutyrate and large urine ketones cannot be explained by volume depletion alone and indicates ketoacidosis.

❌ B. Diabetic ketoacidosis with hyperglycemia
Classic DKA typically requires glucose >250 mg/dL — this patient's glucose is only 192. The scenario describes euglycemic DKA, the signature SGLT2 complication.

❌ C. Alcoholic ketoacidosis
Alcoholic ketoacidosis occurs after heavy alcohol use with minimal food intake. The case specifies SGLT2 exposure and does not mention alcohol. AKA is also typically associated with normal-to-low glucose and heavy beta-hydroxybutyrate, but the drug context makes euglycemic DKA the far better answer.

:::danger
Euglycemic DKA pearl: any patient on an SGLT2 inhibitor presenting with nausea, vomiting, abdominal pain, or tachypnea needs a venous blood gas and serum ketones — even if glucose is normal. Hold SGLT2i at least 3 days before surgery, major fasting, or ketogenic diets.
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