Managing capivasertib-induced hyperglycemia: a report of 3 cases

Phosphoinositide 3-kinase/protein kinase B (AKT) pathway inhibition is an important therapeutic strategy for hormone receptor positive and human epidermal growth factor receptor 2 negative advanced breast cancer. Capivasertib, an oral pan-AKT inhibitor, improves progression-free survival in combination with fulvestrant but is frequently associated with hyperglycemia. Despite this recognized adverse effect, consensus management guidelines are lacking. We describe 3 patients who developed capivasertib-associated hyperglycemia, 2 of whom had severe hyperglycemia with alpelisib therapy, a phosphoinositide 3-kinase inhibitor. Hyperglycemia developed early and was marked by postprandial excursions. All patients were treated with insulin-sensitizing therapies. Preemptive initiation or intensification of antihyperglycemic therapy before capivasertib exposure attenuated hyperglycemia severity. These cases highlight the insulin-resistant phenotype of AKT inhibitor-associated hyperglycemia and support early metabolic assessment, postprandial glucose monitoring, and preferential use of insulin-sensitizing therapies to minimize treatment interruption.