Christian Schnell

SGV Meeting 2026 · Scientific Programme

CHUV, Lausanne

• 24 November 2026 · 15:10How Models May Change During Translation
  Abstract

  Alpelisib plus fulvestrant demonstrated a significant progression-free survival benefit versus fulvestrant in patients with PIK3CA-mutated HR+/HER2− advanced breast cancer. Hyperglycemia, an on-target adverse effect of PI3Kα inhibition, can lead to dose modifications, potentially impacting alpelisib efficacy. Here we report blood glucose data from preclinical studies performed in telemetered conscious, stress-free, pair-housed and freely moving normoglycemic and ZDF (Zucker Diabetic Fatty) diabetic rats treated with alpelisib. For the first time, a continuous 24 h data profile on blood glucose could be obtained following treatment with alpelisib, a selective inhibitor of the PI3K isoform alpha in normoglycemic and ZDF diabetic rats. Blood glucose circadian changes in normoglycemic rats significantly differed from those in diabetic animals. Alpelisib daily treatment at a clinically relevant dose in rats induced a drastic glucose increase over 24 h in diabetic rats as compared to normoglycemic rats.

  Animal distress and measurement variability commonly associated with glucose test strips are highly reduced in telemetered rats. This could improve diagnosis accuracy, reduce animal numbers needed to detect significant drug effects and therapy translatability from preclinical models to clinical studies. Any refinements of measurement techniques that reduce research animal distress should answer both the need for high-quality data and the call for improved care and welfare of the animals. Exploiting a novel real-time telemetry device to monitor blood glucose remotely and continuously in conscious, stress-free, pair-housed and freely moving normoglycemic and diabetic rats provides opportunities for such assessments.