Is there a potential association between spironolactone and the risk of new-onset diabetes in a cohort of older patients with heart failure?

Eur J Clin Pharmacol. 2019 Jun;75(6):837-847. doi: 10.1007/s00228-018-02615-8. Epub 2019 Feb 13.

Abstract

Purpose: Some evidence suggests that spironolactone may have a deleterious effect on glucose homeostasis. The objective of this study was to assess whether spironolactone use is associated with a higher risk of developing diabetes in a large cohort of patients with heart failure (HF).

Methods: Two Quebec government administrative databases were used to identify a cohort of hospitalized patients discharged between January 1995 and December 2009 with a primary discharge diagnosis of HF and without secondary discharge diagnosis of diabetes. Patients were categorized as new users of spironolactone and non-users. The primary outcome was defined as new-onset diabetes (NOD) during 5 years of follow-up and was ascertained using ICD codes for diabetes or use of hypoglycemic agents.

Results: Among the 2974 patients that were included in the cohort analysis, 769 were given a new prescription of spironolactone. The incidence rate of NOD was similar among spironolactone users (5.0 per 100 person-years) and non-users (4.9 per 100 person-years). There was no significant association between the use of spironolactone and NOD in the crude, unadjusted model (hazard ratio (HR) 1.01; 95% confidence interval (CI) 0.80-1.28; p = 0.9217), and it remained unchanged in the adjusted Cox proportional hazard model (HR = 0.92; 95% CI = 0.72-1.18; p = 0.5227). The results were consistent with those observed in sensitivity analyses of a 1:3 propensity score-matched cohort (HR = 0.97; CI = 0.76-1.25; p = 0.8169).

Conclusion: We found no evidence supporting the claim that use of spironolactone is associated with a higher risk of diabetes among patients hospitalized for HF.

Keywords: Aldosterone; Diabetes mellitus; Heart failure; Mineralocorticoid receptor; Spironolactone.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Diabetes Mellitus / epidemiology*
  • Diuretics / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Humans
  • Incidence
  • Male
  • Quebec / epidemiology
  • Risk Factors
  • Spironolactone / therapeutic use*

Substances

  • Diuretics
  • Spironolactone