Management strategies for PI3K/AKT inhibitor–induced hyperglycemia in HR+/HER2– metastatic breast cancer: A claims analysis.

Abstract

e13048 Background: PI3K/AKT pathway inhibitors (PI3K/AKTi; alpelisib, inavolisib, and capivasertib) improve outcomes for patients with HR+/HER2– metastatic breast cancer (mBC) and managing potential hyperglycemia is critical to maintaining treatment adherence. Because PI3K/AKT inhibition directly affects insulin signaling, non-insulin antihyperglycemic (AHG) strategies are often preferred. This study describes real-world strategies for hyperglycemia management among patients receiving PI3K/AKTi. Methods: A retrospective cohort study was conducted using the IQVIA PharMetrics Plus database, including adults with mBC who initiated PI3K/AKTi between 05/01/2019 and 03/31/2025. The index date was defined as the first observed claim for a PI3K/AKTi. Patients were categorized by baseline glycemic status during the 6-month pre-index period using ICD-10 diagnosis codes for diabetes (DM), pre-diabetes (Pre-DM), or non-diabetes (Non-DM). DM patients were also required to have ≥1 pre-index AHG claim. Continuous health plan enrollment for ≥6 months prior to index was required; no continuous enrollment requirement was applied post-index. Patients were followed for up to 90 days post-index and censored at the end of the study period, or health plan disenrollment. AHG treatment use before and 90 days after PI3K/AKTi initiation was summarized descriptively, and the difference in % use for each drug class was reported. Results: Among 2,178 patients, 84.3% were Non-DM, 10.7% DM, and 5% Pre-DM at baseline. Prior to PI3K/AKTi initiation, AHG therapy was used by 7.7% of Non-DM and 21.1% of Pre-DM. Following treatment initiation, use of any AHG therapy increased among patients without baseline diabetes (30.2% Non-DM; 30.3% Pre-DM). Based on 90-day absolute percent-point changes from baseline, increases in AHG use among Non-DM patients were observed for biguanides (+26.1), insulin (+7.2), and sulfonylureas (+4.9), with corresponding increases among Pre-DM patients of +22.9, +13.6, and +9.5, respectively. Among patients with baseline diabetes, insulin use increased by 24.4% following initiation, accompanied by a decline in biguanide use (−11.1%) and a modest increase in DPP-4 inhibitor use (+3.9%). Conclusions: In real-world practice, AHG therapy use increased following initiation of PI3K/AKTi, including notable use of insulin among patients with and without baseline diabetes. These findings highlight variability in hyperglycemia management in clinical practice and underscore an opportunity to optimize supportive care during PI3K/AKTi therapy. Results should be interpreted in light of limitations inherent to claims-based analyses, including reliance on ICD-10 diagnosis codes to define diabetic status, which may result in misclassification, particularly among pre-DM patients.