The association between mineralocorticoid receptor antagonist use and diabetes occurrence and progression: A
Mehmet Kanbay1, Mustafa Guldan2, Lasin Ozbek2
1Department of Internal Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkiye.
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.
Insights
Mineralocorticoid receptor antagonists (MRAs) like spironolactone show modest improvements in HbA1c and glucose levels. Finerenone also reduced new-onset diabetes risk, suggesting potential glycaemic benefits of MRAs.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Pharmacology
Background:
- Mineralocorticoid receptor antagonists (MRAs) have inconsistent effects on glucose metabolism and diabetes risk.
- Previous studies lack comprehensive analysis of MRA impact on glycaemic control and diabetes incidence.
Purpose of the Study:
- To conduct a meta-analysis evaluating MRA association with glycaemic profile changes.
- To assess MRA impact on the risk of new-onset diabetes and its progression.
Main Methods:
- Meta-analysis of 20 studies including adult patients on spironolactone, eplerenone, or finerenone.
- Primary outcomes: new-onset diabetes mellitus and HbA1c change.
- Secondary outcome: alterations in glucose levels.
Main Results:
- Spironolactone significantly reduced HbA1c and fasting glucose compared to placebo.
- Finerenone significantly reduced new-onset diabetes risk by 24% in the FINEARTS-HF trial.
- No significant difference in HbA1c change between spironolactone and eplerenone.
Conclusions:
- Spironolactone use demonstrates modest, statistically significant improvements in HbA1c and glucose levels.
- MRAs, particularly finerenone, may offer glycaemic benefits and reduce diabetes risk.
- Further research into MRA mechanisms for glycaemic control is warranted.
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