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SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study

Jiang Li1, Yuefeng Yu1, Ying Sun1

  • 1Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cardiovascular Diabetology
|October 18, 2023
PubMed
Abstract

Insights

Sodium-glucose cotransporter 2 (SGLT2) inhibitors may reduce atrial fibrillation (AF) risk, potentially through effects on lipoprotein particles. Further research is needed to clarify these metabolic mechanisms.

Area of Science:

  • Cardiology
  • Metabolic Medicine
  • Pharmacology

Background:

  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors show potential in reducing atrial fibrillation (AF) risk.
  • The exact metabolic mechanisms underlying this association remain unclear.
  • SGLT2 inhibitors may influence circulating metabolites beyond glucose regulation, impacting AF risk.

Purpose of the Study:

  • To investigate the role of circulating metabolites in mediating the effects of SGLT2 inhibition on AF.
  • To utilize Mendelian randomization (MR) to explore these associations.

Main Methods:

  • A two-sample, two-step MR study was performed.
  • Genetic variants associated with SLC5A2 gene expression and HbA1c were used as instruments for SGLT2 inhibition.
  • Associations between genetically predicted SGLT2 inhibition, circulating metabolites, and AF were analyzed.

Main Results:

  • Genetically predicted SGLT2 inhibition was associated with a reduced risk of AF (OR=0.51, P=0.039).
  • Two metabolites, total lipoprotein particles and HDL particles, were identified as potential mediators.
  • Lipoprotein particle concentrations mediated 8.03% and HDL particles mediated 7.59% of the SGLT2 inhibition effect on AF.

Conclusions:

  • SGLT2 inhibition is associated with a lower risk of AF.
  • Circulating lipoprotein particle concentrations, particularly HDL, may mediate this protective effect.
  • Further studies are warranted to elucidate the role of blood lipids in the SGLT2 inhibition-AF relationship.
Keywords:
Atrial fibrillationCirculating metabolitesMendelian randomizationSodium-glucose cotransporter 2 inhibition

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