Combination therapy with finerenone and SGLT2 inhibitors significantly reduced all-cause mortality (OR 0.58) compared with finerenone monotherapy in patients with chronic kidney disease.
Meta-Analysis (n=71,567)
Does combination therapy with finerenone and SGLT2 inhibitors improve survival and reduce cardiorenal events in patients with diabetic CKD compared to monotherapy?
Combining finerenone with SGLT2 inhibitors in diabetic CKD improves survival and reduces cardiorenal events compared to finerenone alone, but increases hyperkalemia risk compared to SGLT2i alone.
Effect estimate: OR 0.58 (95% CI 0.36-0.93)
p-value: p=0.02
Background Sodium-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. Methods We 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. Results A 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. Conclusion Combining 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 Registration https: //www. crd. york. ac. uk/prospero/displayᵣecord. php? ID=CRD420251023918, identifier: CRD420251023918.
Wen et al. (Wed,) conducted a meta-analysis in Chronic kidney disease (n=71,567). Combined finerenone and SGLT2 inhibitors vs. Finerenone monotherapy or SGLT2i monotherapy was evaluated on All-cause mortality (OR 0.58, 95% CI 0.36-0.93, p=0.02). Combination therapy with finerenone and SGLT2 inhibitors significantly reduced all-cause mortality (OR 0.58) compared with finerenone monotherapy in patients with chronic kidney disease.