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Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Primary Aldosteronism

Li-Yang Chang1, Chieh Huang1, Ching-Chun Su2

  • 1School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Clinical Journal of the American Society of Nephrology : CJASN
|July 28, 2026
PubMed
Abstract

Insights

Adding sodium-glucose cotransporter-2 (SGLT2) inhibitors to mineralocorticoid receptor antagonists (MRA) significantly lowers mortality and cardiorenal events in primary aldosteronism (PA) patients. This combination therapy shows promise for improving long-term outcomes in this high-risk group.

Area of Science:

  • Endocrinology
  • Cardiology
  • Nephrology

Background:

  • Primary aldosteronism (PA) increases risks for cardiovascular and kidney disease.
  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer cardiorenal protection.
  • This study examines SGLT2 inhibitors combined with mineralocorticoid receptor antagonists (MRA) in PA patients.

Purpose of the Study:

  • To investigate the association of SGLT2 inhibitors with improved outcomes in PA patients treated with MRAs.
  • To evaluate the impact of combined SGLT2 inhibitor and MRA therapy on mortality and cardiorenal events.

Main Methods:

  • Retrospective analysis of TriNetX data (2014-2025) with incident cohort design.
  • Adult PA patients on MRAs were divided into SGLT2 inhibitor users and non-users.
  • Propensity score matching (PSM) was used to compare outcomes, including all-cause mortality, MACE, and MAKE.

Main Results:

  • In the matched cohort (2,507 users vs. 2,507 non-users), SGLT2 inhibitor use was linked to reduced all-cause mortality (aHR 0.59).
  • Combined therapy also showed lower risks for major adverse cardiovascular events (MACE) (aHR 0.81) and major adverse kidney events (MAKE) (aHR 0.58).
  • Kaplan-Meier curves indicated significant early divergence and sustained separation for all outcomes.

Conclusions:

  • Adding SGLT2 inhibitors to MRAs in PA patients is associated with decreased mortality and cardiorenal complications.
  • This combination strategy warrants further evaluation for improving long-term outcomes in high-risk PA populations.
Keywords:
ESKDSGLT2 inhibitorsaldosteronecardiovascular eventscohort studiesdiabetes mellitusdiureticsmortalityoutcomes

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