SynthesisFrontiers in pharmacology2026
Efficacy and safety of novel non-steroidal mineralocorticoid receptor antagonists in diabetic kidney disease: an updated systematic review and meta-analysis of randomized controlled trials.
Synthesis in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Aims: To evaluate the efficacy and safety of novel non-steroidal mineralocorticoid receptor antagonists (nsMRAs) in diabetic kidney disease (DKD). Methods: Following PRISMA 2020, we searched four databases to 31 July 2026, for randomized controlled trials (RCTs) comparing nsMRAs with placebo in adults with DKD. Pooled estimates used random-effects models, with mean differences (MDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, each with 95% confidence intervals (CIs). Risk of bias was assessed with Cochrane RoB 2, and certainty of evidence with GRADE. Results: Eight RCTs (15,143 patients) were included. nsMRAs reduced log-transformed UACR (MD -0.36 log mg/g, 95% CI -0.44 to -0.28; n = 14,512 from 8 trials, predominantly driven by finerenone (5 of 8 trials), with significant drug-type interaction; P < 0.00001) and systolic BP (MD -4.72 mmHg, 95% CI -8.64 to -0.80; n = 7,538 from 3 trials (6 trials reported systolic BP; only 3 were poolable); predominantly driven by FIGARO-DKD; P = 0.02), but increased serum potassium (MD 0.22 mmol/L, 95% CI 0.16 to 0.29; n = 1,468 from 4 trials (6 trials reported serum potassium; FIDELIO-DKD and FIGARO-DKD excluded); P < 0.00001) and induced early eGFR decline (MD -3.01 mL/min/1.73 m Conclusion: In DKD, nsMRAs may reduce UACR and systolic BP. However, UACR was driven by finerenone with significant drug-type interaction, requiring agent-specific interpretation. Systolic BP was driven by FIGARO-DKD. Furthermore, nsMRAs may increase serum potassium and hyperkalemia risk, although the serum potassium analysis excluded two large trials. nsMRAs may also cause early hemodynamic eGFR decline. Notably, this review assessed only surrogate endpoints and safety outcomes. Several outcomes were supported by only 3-4 trials. Given these limitations and low-to-moderate certainty, findings warrant cautious interpretation and risk-benefit assessment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251072300, identifier CRD420251072300.
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