Effect of Jardiance on glucose uptake into astrocytomas

J Neurooncol. 2024 Sep;169(2):437-444. doi: 10.1007/s11060-024-04746-8. Epub 2024 Jul 22.

Abstract

Purpose: SGLT2, the sodium glucose cotransporter two, is expressed in human pancreatic, prostate and brain tumors, and in a mouse cancer model SGLT2 inhibitors reduce tumor glucose uptake and growth. In this study we have measured the effect of a specific SGLT2 inhibitor, Jardiance® (Empagliflozin), on glucose uptake into astrocytomas in patients.

Methods: We have used a specific SGLT glucose tracer, α-methyl-4-[18F]fluoro-4-deoxy-α-D-glucopyranoside (Me4FDG), and Positron Emission Tomography (PET) to measure glucose uptake. Four of five patients enrolled had WHO grade IV glioblastomas, and one had a low grade WHO Grade II astrocytoma. Two dynamic brain PET scans were conducted on each patient, one before and one after treatment with a single oral dose of Jardiance, a specific SGLT2 inhibitor. As a control, we also determined the effect of oral Jardiance on renal SGLT2 activity.

Results: In all five patients an oral dose (25 or 100 mg) of Jardiance reduced Me4FDG tumor accumulation, highly significant inhibition in four, and inhibited SGLT2 activity in the kidney.

Conclusions: These initial experiments show that SGLT2 is a functional glucose transporter in astocytomas, and Jardiance inhibited glucose uptake, a drug approved by the FDA to treat type 2 diabetes mellitus (T2DM), heart failure, and renal failure. We suggest that clinical trials be initiated to determine whether Jardiance reduces astrocytoma growth in patients.

Keywords: Glioblastoma; Me4FDG; PET; SGLT2; SGLT2i.

MeSH terms

  • Aged
  • Astrocytoma* / diagnostic imaging
  • Astrocytoma* / drug therapy
  • Astrocytoma* / metabolism
  • Astrocytoma* / pathology
  • Brain Neoplasms* / diagnostic imaging
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / pathology
  • Female
  • Fluorodeoxyglucose F18
  • Glucose* / metabolism
  • Glucosides / pharmacology
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography*
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Sodium-Glucose Transporter 2* / metabolism

Substances

  • Glucose
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sodium-Glucose Transporter 2
  • Glucosides
  • SLC5A2 protein, human
  • Fluorodeoxyglucose F18