Ketoacidosis With Canagliflozin Prescribed for Phosphoinositide 3-Kinase Inhibitor–Induced Hyperglycemia: A Case Report

Context. Many phosphoinositide-3-kinase (PI3K) inhibitors are under trial for cancer treatment. We present a patient taking taselisib who developed ketoacidosis within 1 week of starting canagliflozin. Case Description. A 69-year-old female patient with no previous history of diabetes mellitus was enrolled in a clinical trial for taselisib therapy in stage IV breast cancer. Hyperglycemia treatment with metformin was insufficient and not tolerated. The addition of canagliflozin daily resulted in ketoacidosis and hospitalization within 1 week. Conclusions. This case report brings together 2 poorly understood and relatively understudied disorders of glucose homeostasis: hyperglycemia due to PI3K inhibition and euglycemic ketoacidosis due to dehydration/SGLT2 inhibition. It demonstrates the complexities of glucose management in the setting of PI3K inhibition. PI3K stimulation (via insulin) in this setting is counterintuitive; therefore, non-insulin-mediated therapies (eg, metformin, thiazolidinediones) might be favored over insulin-mediated therapies.