Capivasertib, an AKT (protein kinase B) inhibitor, in combination with fulvestrant, reduces the risk of progression in recurrent breast cancer; however, it frequently leads to hyperglycemia by disrupting the insulin signaling pathways. Insulin-based therapies are generally ineffective in this setting and may worsen cancer outcomes. Herein, we report a case of capivasertib-induced diabetes successfully managed with insulin-independent glucose-lowering agents while capivasertib therapy was continued. A 57-year-old female with a body mass index of 23.0 kg/m² developed hyperglycemia one month after initiating capivasertib, with a glycosylated hemoglobin (HbA1c) level of 7.3%. A 75-g oral glucose tolerance test (OGTT) confirmed the diagnosis of diabetes according to the American Diabetes Association diagnostic criteria, demonstrating a fasting glucose level of 173 mg/dL, a two-hour glucose level of 512 mg/dL, and marked hyperinsulinemia. The markedly elevated glucose levels observed during the OGTT likely reflect severe drug-induced hyperglycemia associated with AKT inhibition, rather than a typical OGTT response in untreated diabetes. Treatment with empagliflozin (10 mg/day, a sodium-glucose cotransporter-2 inhibitor) and voglibose (0.4 mg/day, an alpha-glucosidase inhibitor) improved the HbA1c level to 6.3% within two months. After five months, a repeat OGTT showed improvement, shifting from the level of diabetes to impaired glucose tolerance, with substantially reduced insulin levels. This case may represent one of the early reports describing the successful management of capivasertib-induced diabetes with insulin-independent glucose-lowering agents, suggesting a potential strategy for managing AKT inhibitor-induced hyperglycemia.
Takeda et al. (Sat,) studied this question.