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

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 (DKA) and hyperosmolar hyperglycemic state (HHS) following treatment with capivasertib.

A 59-year-old female with history of obesity (body mass index 39 kg/m² ref: 18.5 - 24.9 kg/m²), 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 1 week prior to hospitalization, was 5.6% (ref: <5.7%). She was diagnosed with mixed DKA and 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. She ultimately recovered without requiring any antihyperglycemic therapy.

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.

Capivasertib can induce DKA/HHS and refractory hyperglycemia in nondiabetic 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.