Diabetic ketoacidosis induced by Alpelisib: A case report on a rare complication requiring emergency management

Alpelisib is a PI3K inhibitor used for the treatment of hormone receptor-positive (HR+), HER2-negative advanced breast cancer with a PIK3CA mutation. Hyperglycemia is its most common adverse effect, which can rarely lead to life-threatening complications such as diabetic ketoacidosis (DKA). This complication can develop even in patients with no prior history of diabetes and requires rapid intervention in the emergency department (ED). A 62-year-old female patient presented to the ED with complaints of reduced oral intake, fatigue, and oral sores 15 days after initiating alpelisib therapy. Laboratory investigations revealed severe hyperglycemia (593.9 mg/dL), metabolic acidosis (pH 7.159, HCO 3 - 6.8 mmol/L), positive urinary ketones, and an HbA1c level of 9.4%, suggesting previously undiagnosed diabetes. A prompt diagnosis was made of alpelisib-induced DKA in a patient with previously undiagnosed diabetes mellitus. Her acidosis resolved on the second day of admission. While hyperglycemia is observed in patients treated with alpelisib, the incidence of Grade 3–4 hyperglycemia is 36.6%, emerging within the first few weeks of treatment. The incidence of DKA is low (0.7%) but is a life-threatening condition. The underlying mechanism is attributed to severe insulin resistance and increased hepatic gluconeogenesis due to the inhibition of the PI3K/AKT pathway. This case report underscores that alpelisib therapy can precipitate DKA, especially in patients with underlying, potentially undiagnosed, diabetes. A multidisciplinary approach, including close glycemic monitoring, assessment of risk factors, and preparedness for hyperglycemic emergencies, is critical for patients starting alpelisib.