MON-588 Capivasertib-Induced Severe Hyperglycemia Refractory to Insulin Therapy

Abstract Disclosure: K. Mitrollari: None. A. Abusamha: None. M.S. Kazi: None. U. Tarabichi: None. M.H. Kazi: None. Background: Mild hyperglycemia is a relatively common side effect of capivasertib, however severe hyperglycemia only occurred in 2.8% of patients during clinical trials. We present a case of a patient with severe refractory hyperglycemia while undergoing capivasertib therapy. Clinical Case: An 86 y/o F with T2DM, hypothyroidism, breast cancer, and prior CVA presented with acute right thalamic stroke and serum glucose of 168 mg/dL. She required ∼10 Units of insulin/day initially to control her blood glucose (BG). Her A1c was 6.8%. On day four of admission, oncology resumed capivasertib and six hours later BG increased to 382 mg/dL on fingerstick. She was started on a regular insulin infusion with BG ranging 370-569 mg/dL on the maximum infusion rate. Subcutaneous basal-bolus insulin was added with total daily dose of ∼800-900 Units/day. Metformin 500 mg twice daily and pioglitazone 30 mg daily were also prescribed to improve insulin sensitivity. Despite discontinuation of capivasertib, hyperglycemia persisted until twelve hours later, when the patient’s BG began to progressively decrease, reaching 153 mg/dL 24 hours later. The patient then experienced hypoglycemia with lowest BG 39 mg/dL requiring IV dextrose and 5% dextrose infusion initially started at 50 mL/hour and gradually increased to 200 mL/hour. Hypoglycemia resolved 36 hours after the last insulin glargine administration. Throughout capivasertib therapy, daily chemistry panels showed bicarbonate within normal limits. Discussion: Capivasertib is an AKT inhibitor used to treat hormone receptor-positive breast cancer. Overactivation of the AKT pathway can lead to cancer, making an AKT-inhibitor a great treatment option. However, the AKT pathway regulates glucose metabolism by promoting GLUT4 translocation for glucose uptake, activating glycogen synthesis, enhancing glycolysis, and inhibiting gluconeogenesis. Inhibiting these mechanisms then leads to hyperglycemia. Clinicians should be aware of this potential adverse effect, especially in patients with preexisting metabolic disorders or risk factors for insulin resistance. Although the median time to first occurrence of hyperglycemia was 15 days during the clinical phase trials, we observed an immediate effect of hyperglycemia in our patient as well as immediate resolution after discontinuation of capivasertib. In addition to discontinuing the offending agent, treating AKT inhibition involves administration of insulin and insulin sensitizers, such as metformin and pioglitazone. Early recognition, glucose monitoring, and proactive management are crucial to prevent complications. This case highlights the need for further research on AKT-targeted therapies and metabolic side effects in patients with diabetes mellitus. We recommend considering other therapies in patients with diabetes mellitus as capivasertib can lead to catastrophic metabolic disturbances. Presentation: Monday, July 14, 2025