SGLT2 inhibitors promote glucosuria by inhibiting renal glucose reabsorption, leading to reduced serum glucose and insulin levels. This disrupt the insulin-to-glucagon ratio, promoting glucagon release and triggering counter-regulatory hormones such as catecholamines and cortisol. During metabolic stress like surgery, this can lead to lipolysis and beta oxidation of free fatty acids in the liver and eventually production of ketones. SGLT2 inhibitors further exacerbate this process by directly stimulating pancreatic glucagon secretion, increasing the risk of Euglycemic Diabetic Ketoacidosis (EDKA).

A 60-year-old diabetic male on empagliflozin, recently diagnosed with triple-vessel coronary artery disease, underwent coronary artery bypass graft (CABG) surgery. SGLT2 inhibitor was withheld two days prior to surgery but was resumed on postoperative day (POD) 6. On POD 7, patient developed nausea, vomiting, anorexia, dyspnea, and loss of consciousness. Laboratory tests revealed: urine ketones 100mg/dL, arterial pH 7.03, bicarbonate 3 mEq/L, glucose 141 mg/dL, osmolality 307 mOsm/kg, potassium 3.57 mEq/L, and anion gap 31.2. Infectious causes were ruled out, and a diagnosis of EDKA was made.

Empagliflozin was discontinued; the patient was managed with D5 0.45% NaCl with potassium supplementation and an insulin drip titrated to hourly capillary glucose levels. His symptoms resolved, and he was transitioned to subcutaneous long-acting and pre-meal rapid acting insulin.

EDKA is a potentially life-threatening complication in both Type 1 and Type 2 diabetes. It is characterized by normal or mildly elevated glucose (<250 mg/dL), severe metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L), and ketonemia. Prompt recognition and treatment are essential. Delay in diagnosis and inadequate treatment, especially hydration and omission of insulin infusion during management, can prolong acidosis and hospitalization.