SGLT2 inhibition improves PI3Kα inhibitor-induced hyperglycemia: findings from preclinical animal models and from patients in the BYLieve and SOLAR-1 trials.

ABSTRACT:

Purpose

Alpelisib plus fulvestrant demonstrated a significant progression-free survival benefit versus fulvestrant in patients with PIK3CA-mutated HR+ /HER2- advanced breast cancer (ABC) (SOLAR-1). Hyperglycemia, an on-target adverse effect of PI3Kα inhibition, can lead to dose modifications, potentially impacting alpelisib efficacy. We report data from preclinical models and two clinical trials (SOLAR-1 and BYLieve) on Sodium glucose cotransporter 2 inhibitor (SGLT2i) use to improve PI3Kα inhibitor-associated hyperglycemia.

Methods

Healthy Brown Norway (BN), mild diabetic Zucker diabetic fatty (ZDF), and Rat1-myr-p110α/HBRX3077 tumor-bearing nude rats treated with alpelisib were analyzed for glucose and insulin control with metformin and dapagliflozin (SGLT2i) and alpelisib

SUBMITTER: Borrego MR 

PROVIDER: S-EPMC11452482 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature