Capivasertib-Induced Refractory Hyperglycemia in a Nondiabetic Patient With Metastatic Breast Cancer

Background/ Objective: Selective AKT inhibitors such as capivasertib are approved to treat hormone receptor-positive, HER2-negative advanced breast cancer.Hyperglycemia is a known side effect of these agents, however, severe hyperglycemia is uncommon.We describe a patient without known history of diabetes who developed a rare presentation of refractory, severe hyperglycemia with mixed diabetic ketoacidosis and hyperosmolar hyperglycemic state following treatment with capivasertib.Case Presentation: A 59-year-old female with history of obesity (BMI 39 kg/m 2 ref: 18.5 -24.9 kg/m 2 ), metastatic breast cancer, and stage 4 chronic kidney disease was found unresponsive at home after developing nausea and vomiting, on day 7 of capivasertib therapy.She had no known prior history of diabetes; the most recent HbA1c, obtained one week prior to hospitalization, was 5.6% (ref: <5.7%).She was diagnosed with mixed diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) with capillary blood glucose levels exceeding 1200 mg/dL (ref: 70-99 mg/dl).Despite high-dose insulin (>40 units/hour), her hyperglycemia remained refractory until initiation of continuous renal replacement therapy (CRRT).She ultimately recovered without requiring any antihyperglycemic therapy. Discussion:While hyperglycemia is a known potential side effect of capivasertib, DKA, HHS, and refractory hyperglycemia are rare.Potential risk factors for this presentation include obesity, acute renal failure, and hemodynamic instability. Conclusion:Capivasertib can induce DKA/HHS and refractory hyperglycemia in non-diabetic patients.Prompt recognition, intensive management, and drug discontinuation are critical.This is one of the first case reports to describe sustained euglycemia following severe and refractory hyperglycemia due to capivasertib therapy.