Br J Clin Pharmacol. 2025 Dec 30. doi: 10.1002/bcp.70433. Online ahead of print.
ABSTRACT
BACKGROUND AND AIM: Mineralocorticoid receptor antagonists (MRAs) effects on glucose metabolism and diabetes risk are inconsistently reported. We conducted a meta-analysis to evaluate the association between MRA use and glycaemic profile change as well as the risk of diabetes occurrence and progression.
METHODS: Eligible studies enrolling adult patients receiving spironolactone, eplerenone or finerenone for any clinical indication were included. The primary outcomes were new-onset diabetes mellitus and change in HbA1c (%) levels. A secondary outcome was alterations in glucose levels.
RESULTS: This meta-analysis of 20 studies evaluated the effects of MRAs on glycaemic parameters. Spironolactone significantly reduced endpoint HbA1c (%) compared to placebo (mean difference -0.27%, 95% CI: -0.38 to -0.15; P < 0.00001; I2 = 31%) and in change-from-baseline fasting glucose (-0.24 mmol/L, 95% CI: -0.27 to -0.21; P < 0.00001; I2 = 0%) over 4-24 weeks. Similarly, change-from-baseline HbA1c (%) was significantly lowered (-0.19%, 95% CI: -0.29 to -0.08; P = 0.0004; I2 = 33%). In a head-to-head comparison, spironolactone and eplerenone showed no significant difference in HbA1c (%) change (-0.03%, 95% CI: -0.50 to 0.43; P = 0.89; I2 = 88%). In the FINEARTS-HF trial, finerenone significantly reduced the risk of developing new-onset diabetes by 24%. Lastly, finerenone was associated with slightly lower rates of insulin initiation (8.1% vs. 9.0%) and escalation in glucose-lowering medication classes (32.1% vs. 34.0%) compared to placebo.
CONCLUSIONS: Spironolactone use is associated with modest but statistically significant improvements in HbA1c and glucose levels compared to placebo, suggesting a potential glycaemic benefit.
PMID:41469771 | DOI:10.1002/bcp.70433
