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Spironolactone and New-Onset Diabetes in Heart Failure: A Post Hoc Analysis of the TOPCAT Trial

Dung Viet Nguyen1, Hoai Thi Thu Nguyen1

  • 1Department of Cardiology, Faculty of Medicine, VNU University of Medicine and Pharmacy, Hanoi, Vietnam; Vietnam National Heart Institute, Bach Mai Hospital, Hanoi, Vietnam.

JACC. Asia
|June 12, 2026
PubMed

Insights

Spironolactone did not significantly increase new-onset diabetes risk in heart failure patients. Further research is needed due to wide confidence intervals and potential subgroup variations in diabetes risk.

Area of Science:

  • Cardiology
  • Endocrinology
  • Clinical Trials

Background:

  • Mineralocorticoid receptor antagonist therapy effects on new-onset diabetes risk are inconsistent.
  • Spironolactone is a commonly used mineralocorticoid receptor antagonist.

Purpose of the Study:

  • To investigate the association between spironolactone use and the incidence of new-onset diabetes.
  • To analyze data from the TOPCAT trial for spironolactone's effect on diabetes risk in heart failure patients.

Main Methods:

  • Post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled TOPCAT trial.
  • Included patients with heart failure and ejection fraction ≥45% without baseline diabetes.
  • Used Fine-Gray competing-risks regression, treating death as a competing event.

Main Results:

  • Spironolactone was not significantly associated with new-onset diabetes compared to placebo (adjusted sHR: 1.26; 95% CI: 0.64-2.50).
  • Findings were consistent across different populations and sensitivity analyses.
  • Subgroup analyses indicated a nonsignificant trend toward increased risk in patients with higher blood pressure, prediabetes, higher BMI, or former smoking status.

Conclusions:

  • Spironolactone did not significantly impact new-onset diabetes risk in patients with heart failure with mildly reduced or preserved ejection fraction.
  • Wide confidence intervals and potential subgroup heterogeneity suggest further investigation is warranted.
Abstract

Keywords:
HFmrEFHFpEFdiabetesheart failuremineralocorticoid receptor antagonistspironolactone

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