Cardiorenal protection and safety of finerenone-based treatment on a background of standard therapy in diabetic kidney disease: an updated systematic review and meta-analysis of randomized controlled trials

Objective Previous meta-analyses evaluated finerenone in diabetic kidney disease (DKD) but used heterogeneous dose inclusion criteria and lacked contemporary evidence. More importantly, no synthesis has specifically examined finerenone-based treatment on a background of standard therapy. To address these gaps, we conducted an updated systematic review and meta-analysis to evaluate the efficacy and safety of finerenone-based treatment on a background of standard therapy in DKD. Methods Following PRISMA 2020 guidelines, we searched PubMed (NCBI), Web of Science Core Collection (Clarivate), Embase.com (Elsevier), and the Cochrane Library (Wiley) from inception to June 12, 2026, for randomized controlled trials (RCTs) comparing finerenone at 10, 15, or 20 mg once daily versus placebo, with both treatments administered on a background of standard therapy in adults with DKD. Random-effects models were used to pool hazard ratios (HRs) for time-to-event outcomes, risk ratios (RRs) for adverse events, and weighted mean differences (WMDs) for continuous outcomes, with all pooled estimates reported with 95% confidence intervals (CIs). The risk of bias was assessed using the Cochrane RoB 2.0 tool. Meta-analyses were conducted using Stata 16. Results Six RCTs involving 14,147 patients were included: five trials comparing finerenone with placebo and one trial comparing finerenone plus empagliflozin with empagliflozin plus placebo, all on a background of standard therapy. Finerenone-based treatment reduced the primary composite kidney outcome (HR 0.84, 95% CI 0.77–0.92) and the composite cardiovascular outcome (HR 0.87, 95% CI 0.79–0.95). All-cause mortality was numerically lower with finerenone-based treatment but was not statistically significant (HR 0.89, 95% CI 0.80–1.00). Finerenone-based treatment also reduced UACR (ln(GMR) − 0.37, 95% CI − 0.40 to − 0.35) and systolic blood pressure (WMD − 3.72, 95% CI − 4.28 to − 3.17), while increasing serum potassium (WMD 0.20, 95% CI 0.15–0.26) and causing an early decline in eGFR (WMD − 2.44, 95% CI − 2.82 to − 2.06). In safety analyses, the risk of hyperkalemia was higher with finerenone-based treatment (RR 1.91, 95% CI 1.71–2.12), whereas the overall incidence of adverse events did not differ (RR 1.00, 95% CI 0.97–1.03). Conclusions On a background of standard therapy, finerenone-based treatment was associated with significant reductions in the primary composite kidney outcome and the cardiovascular outcome in patients with DKD. These long-term benefits are supported mainly by the pivotal FIDELIO-DKD and FIGARO-DKD trials. However, early eGFR decline (likely a hemodynamic effect) and increased hyperkalemia necessitate close monitoring. In addition, evidence regarding an incremental hard-outcome benefit when finerenone is combined with SGLT2 inhibitors remains limited, and this combination strategy requires confirmation in adequately powered trials.