Alpelisib-Induced Hyperglycemic Emergencies

Background: Hyperglycemia is the commonest adverse effect of the anti-cancer drug alpelisib, an inhibitor of phosphatidylinositol-3-kinase (PI3K). Main objective: To describe a woman presenting with alpelisib-induced hyperglycemic emergency and other similar cases reported in the literature. Secondary objective: To discuss the status of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, ketogenic diet and insulin for alpelisib-induced hyperglycemia. Methods: Pubmed research up to May 2, 2023. Search terms included alpelisib, hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state, SGLT-2 inhibitors, ketogenic diet, insulin. Clinical trials, case reports, pertinent review articles and animal studies, and pre-print articles were reviewed. Results: 17 cases of hyperglycemic emergencies, including ours, were described. Nine cases presented with diabetic ketoacidosis (DKA) and 2 cases with mixed DKA and hyperosmolar hyperglycemic state (HHS). Six of the 17 patients (35%) had no history of diabetes. Median time from initiation of alpelisib to diagnosis of hyperglycemic emergency was 2 weeks (range 7-69 days). All patients were treated successfully with intravenous (IV) fluids and insulin. In 2 patients, DKA recurred 4 h and 5 days after re-starting alpelisib. Anecdotal data suggest that use of SGLT-2 inhibitors and ketogenic diet might be effective in controlling alpelisib-induced hyperglycemia. Yet, these 2 treatment strategies may predispose to DKA. Animal studies suggest that exogenous insulin might decrease the anti-tumor efficacy of alpelisib. Conclusions: Alpelisib-induced hyperglycemia can proceed to hyperglycemic crises even in patients without history of diabetes. Physicians and patients should be aware of this complication to avoid any delay in its diagnosis. Until more data become available, SGLT-2 inhibitors and ketogenic diet should be used with extreme caution in alpelisib-induced hyperglycemia.