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

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.