Effects of mineralocorticoid receptor antagonists on cardiometabolic profile and liver health in individuals with increased cardiometabolic risk: a systematic review and meta-analysis of randomized controlled trials

INTRODUCTION: Recent studies link overactivation of mineralocorticoid receptors to insulin resistance, inflammation, and metabolic dysfunction-associated steatotic liver disease. We aimed to assess the effects of mineralocorticoid receptor antagonists (MRAs) on liver steatosis, fibrosis, inflammation, and cardiometabolic risk. METHODS: We conducted a systematic review and meta-analysis including placebo-controlled randomized controlled trials (RCTs) assessing MRAs' effects. A random-effects meta-analysis assessed MRAs effects on anthropometry, lipid profile, inflammatory parameters, and glucose metabolism. Outcomes were presented as mean differences (MD) with 95% confidence intervals (95% CI). Twenty-six studies were included and seventeen were meta-analyzed. MRAs studied included spironolactone, eplerenone, canrenone, apararenone, and finerenone. Most studies included participants with diabetes, metabolic syndrome, obesity, heart failure, or hypertension. RESULTS: In the meta-analysis, we found a mild but significant decrease in body weight (MD = -1.27, 95% CI [-2.54, -0.01]) and a trend for higher HbA1c (MD = 0.13, 95% CI [-0.01, 0.27]) with MRAs. There was a trend toward a decrease in C-reactive protein levels (MD = -0.99, 95% CI [-2.22, 0.24]) with MRAs. RCTs on liver function and structure showed no differences compared to placebo. CONCLUSIONS: MRAs appear to have a mild impact on metabolic and inflammatory parameters in patients with increased cardiometabolic risk. However, more RCTs on MRAs' cardiometabolic impact are needed. REGISTRATION: This study was registered with PROSPERO (CRD42025632202).