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Updated: Sep 19, 2025

Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
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Genomic insights about the effect of sodium-glucose cotransporter 2 inhibitors: a systematic review

Pavitraa Saravana Kumar1, Yogapriya Chidambaram1, G Shree Devi2

  • 1Department of Clinical Research, Sri Ramachandra Institute of Higher Education and Research (SRIHER), Chennai, Tamil Nadu, India.

Frontiers in Genetics
|June 16, 2025
PubMed

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce inflammation and improve heart failure (HF) outcomes by modulating gene expression. These findings suggest personalized treatment pathways for HF patients based on genomic insights.

Area of Science:

  • Cardiovascular Medicine
  • Genomics
  • Pharmacology

Background:

  • Heart failure (HF) presents a significant global health burden with limited effective treatments.
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially for diabetes, show promise in reducing HF hospitalizations and mortality.

Purpose of the Study:

  • To systematically review the genomic effects of SGLT2 inhibitors in heart failure patients.
  • To explore gene expression, inflammatory biomarkers, and potential personalized treatment strategies.

Main Methods:

  • Systematic literature search adhering to PRISMA guidelines up to November 2024.
  • Inclusion of studies investigating genomic or molecular impacts of SGLT2 inhibitors in HF.
  • Data extraction and analysis focused on gene expression, biomarkers, and genomic mechanisms.

Main Results:

  • SGLT2 inhibitors downregulate pro-inflammatory genes in adipose tissue, reducing inflammation and ferroptosis.
  • CXCL10 identified as a key mediator of anti-inflammatory effects, linked to reduced HF risk.
  • LRRTM2 identified as a critical mediator with genetic links to reduced HF risk via SGLT2 inhibition.

Conclusions:

  • SGLT2 inhibitors exert cardiovascular benefits through genomic mechanisms, including gene expression modulation.
  • Insights into protein interactions and gene expression pathways offer potential for personalized HF treatment.
  • Further large-scale studies are required to validate these genomic mechanisms and clinical implications.
Abstract

Keywords:
gene expressiongenomicsheart failureinflammatory biomarkersodium-glucose cotransporter 2 inhibitors

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