SAT-572 - On-Day High, Off-Day Low: CGM Reveals Cyclic Dysglycemia from Capivasertib (AKT Inhibitor)

Introduction:
AKT inhibitors like capivasertib have been linked to hyperglycemia and severe glycemic events, including DKA and HHS, in nondiabetic patients. By blocking AKT, they interfere with insulin signaling, causing insulin resistance. We present a woman in her 60's, with stage IV breast cancer who developed new-onset hyperglycemia despite a normal baseline HbA1c.

Case Presentation:
A Female in her 60s, with a history of stage IV invasive lobular breast cancer, hormone receptor positive (ER >50%, PR 10–15%), HER2 2+/FISH negative, presented for evaluation of new-onset hyperglycemia. She has a history of Hashimoto thyroiditis on levothyroxine 75 μg daily and vitamin D deficiency on weekly supplementation. Her family history was notable for diabetes in her son and aunt. She was originally diagnosed with breast cancer at age 50, treated with mastectomy, adjuvant chemotherapy (doxorubicin, cyclophosphamide, paclitaxel), and palliative radiation to metastatic bone lesions. She experienced recurrence two years later with PIK3CA-mutated disease & was started on the AKT inhibitor capivasertib 200 mg BID four days per week. Baseline HbA1c was 5.3%, with no prior diabetes. A month later, routine labs showed an HbA1c of 6.6%, prompting endocrinology referral. She was started on metformin 500 mg BID and counseled on diet and glucose monitoring using a CGM. She reported postprandial glucose spikes up to 400 mg/dL on treatment days and mild asymptomatic hypoglycemia on non-treatment days. She continues capivasertib therapy while adhering to lifestyle modifications, CGM monitoring, and endocrinology follow-up, highlighting the importance of early recognition and management of AKT inhibitor related hyperglycemia.

Conclusion:
This case highlights AKT inhibitor associated hyperglycemia as an important and increasingly recognized side effect. Our patient developed new-onset hyperglycemia shortly after starting capivasertib despite a normal baseline HbA1c and no prior history of diabetes, consistent with drug-induced insulin resistance from AKT pathway inhibition. Continuous glucose monitoring showed postprandial hyperglycemia on treatment days and relative hypoglycemia on non-treatment days, reflecting the effects of the medication. Early endocrinology involvement, dietary changes, and use of metformin allowed continuation of cancer therapy while reducing metabolic complications. Clinicians should closely monitor glucose levels in patients receiving AKT inhibitors and provide timely management.

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