The association between mineralocorticoid receptor antagonist use and diabetes occurrence and progression: A systematic review and meta-analysis

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; I-2 = 31%) and in change-from-baseline fasting glucose (-0.24 mmol/L, 95% CI: -0.27 to -0.21; P < 0.00001; I-2 = 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; I-2 = 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; I-2 = 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.