Combining finerenone with SGLT2 inhibitors lowers mortality and cardiovascular events in diabetic chronic kidney disease patients

BackgroundSodium-glucose cotransporter two inhibitors (SGLT2is) and finerenone have demonstrated individual efficacy in reducing cardiorenal events among patients with diabetic chronic kidney disease (CKD). However, the additive benefits and safety profile of combining these agents remain unclear.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing finerenone plus SGLT2is versus monotherapy. Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACEs), kidney-specific composite outcomes, and hyperkalemia risk. Pooled odds ratios (OR) and 95% confidence intervals (CIs) were calculated using a random-effects model.ResultsA total of eight studies (N = 1,580) were included. Compared with finerenone monotherapy, combination therapy significantly reduced all-cause mortality (OR 0.58; 95% CI: 0.36–0.93). Furthermore, combination therapy also reduced MACE risk (OR 0.70; 95% CI: 0.51–0.97) and major adverse kidney event (MAKE) risk (OR 0.63; 95% CI: 0.44–0.89) compared with finerenone monotherapy. Combination therapy significantly reduced urinary albumin–creatinine ratio (UACR) more than finerenone monotherapy, with a mean difference of 0.10 (equivalent to a 10% greater reduction; combination vs. finerenone, 95% CI: 0.00–0.19; p = 0.045). However, the combined group had a higher risk of hyperkalemia compared to SGLT2i monotherapy (OR 3.00; 95%: CI 2.50–3.61). No significant benefit was observed in composite kidney outcomes compared with SGLT2 inhibitors alone.ConclusionCombining finerenone with SGLT2i may improve survival and reduced risks of MACEs and MAKEs compared with finerenone monotherapy in patients with diabetic CKD. These findings support careful consideration of dual therapy, especially in high-risk populations.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251023918, identifier: CRD420251023918.