Inavolisib-induced fulminant-like diabetes and hyperosmolar hyperglycemic state: a case report

Inavolisib, a recently approved phosphatidylinositol 3-kinase α (PI3Kα) inhibitor for advanced breast cancer, carries a notable risk of hyperglycemia. Despite this established, on-target adverse effect, clinical endocrinologists often lack sufficient awareness regarding both the risk profile and the specific management strategies required for Inavolisib-induced hyperglycemia. The objective of this report is to describe a patient with fulminant-like diabetes accompanied by Hyperosmolar Hyperglycemic State (HHS) following Inavolisib administration.

A 59-year-old female patient with metastatic breast cancer developed rapid-onset and severe hyperglycemia (blood glucose: 48.0 mmol/L at emergency presentation) progressing to HHS within 72 hours of initiating Inavolisib therapy. She presented with fatigue but showed no evidence of ketoacidosis. She had no personal or family history of diabetes mellitus and multiple prior random blood glucose measurements were within normal range. Admission laboratory findings included glycated hemoglobin A1c (HbA1c) 5.7% (reference: 4.0-6.0%), fasting plasma glucose 8.6 mmol/L, fasting insulin 41.5 μU/mL (reference: 2.6-24.9 μU/mL), and fasting C-peptide 10.2 ng/mL (reference: 1.1-4.4 ng/mL), Diabetes-related autoantibodies (ICA, GADA, IAA) were negative. After discontinuation of Inavolisib and administration of intensive insulin therapy, the patient's hyperglycemia resolved rapidly.

Inavolisib-induced hyperglycemia may occur abruptly after treatment initiation and can rapidly progress to severe hyperglycemic emergencies such as HHS, even in patients without known dysglycemia. Normal baseline glycemic indices do not reliably exclude the risk of severe toxicity. Early metabolic assessment, close glucose monitoring, prompt interruption of inavolisib when clinically indicated, and rapid insulin-based management are essential for timely recognition and safe clinical care.