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

Abstract

The renin-angiotensin-aldosterone system regulates blood pressure and fluid balance. Recent studies link overactivation of mineralocorticoid receptors to insulin resistance, inflammation and metabolic dysfunction-associated steatotic liver disease. With the rising use of mineralocorticoid receptor antagonists (MRA), we assessed their effects on liver steatosis, fibrosis, metabolism, and inflammation in cardiometabolic risk patients. We conducted a systematic review and meta-analysis including placebo-controlled randomized controlled trials (RCTs) assessing the effects of MRA. The literature search was conducted in Pubmed and Web of Science. A random-effects meta-analysis assessed MRA effects on lipid profile, inflammatory parameters, anthropometry and glucose metabolism. Outcomes were presented as mean differences (MD) with 95% confidence intervals. We included twenty-six studies in the review, with seventeen in the meta-analysis. MRAs studied included spironolactone, eplerenone, canrenone, apararenone and finerenone. Most participants had diabetes, metabolic syndrome, obesity, heart failure, or hypertension. There was a mild but significant decrease in body weight (MD = -1.27, 95%CI [-2.53, -0.01]; I^2 = 76.89%) and a tendency for HbA1c to increase (MD 0.13, 95%CI [-0.01, 0.27]; I^2=88.24%), without effects on body mass index, HOMA-IR or lipid profile. There was a trend towards a decrease on C-reactive protein levels (MD=-0.99 [-2.22, 0.24]; I^2 = 95.29%). RCTs on liver function, steatosis, and fibrosis showed no difference compared to placebo. MRAs appear to have a mild impact on metabolic and inflammatory parameters in patients with increased cardiometabolic risk. However, due to study heterogeneity, more RCTs on MRAs' metabolic impact are needed.