Abstract 10533: Cardiorenal Effects of Sglt2 Inhibitors and Finerenone in Type 2 Diabetes and Chronic Kidney Disease. Single, Dual or Triple Therapy? A Network Meta-Analysis

Abstract

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and a non-steroidal mineralocorticoid receptor antagonist, finerenone, have demonstrated their efficacy in slowing CKD progression and preventing cardiovascular events in diabetic kidney disease (DKD). However, it is unclear which one is more effective or whether a combination could provide additional benefits. Methods: A network meta-analysis (NMA) was conducted on RCTs of DKD, which evaluated the cardiovascular and renal effects of SGLT2i and finerenone. The primary outcome was a cardiorenal outcome composed of GFR decline as defined in original RCTs, end-stage kidney disease (ESKD), heart failure hospitalization (HHF), and death from renal and cardiovascular causes. Results: This NMA comprised 4 RCTs and 61,609 patient-year with DKD. Dual therapy with SGLT2i+RAASi or finerenone+RAASi was more effective than single therapy with RAAS inhibition (RAASi) for the risk reduction of the cardiorenal composite HR 0.67 (95% CrI 0.60 - 0.74) and 0.81 (95% CrI 0.75 - 0.89), respectively. The dual therapy with SGLT2i+RAASi was superior to finerenone+RAASi HR 0.82 (95% CrI 0.72 - 0.94) for the reduction of cardiorenal events (Table 1). The triple therapy (SGLT2i+finerenone+RAASi) vs RAASi showed a 46% relative risk reduction (HR 0.54 95% CrI 0.5 - 0.58) for the cardiorenal composite. Finerenone+RAASi was most likely to lead to discontinuation of therapy due to hyperkalemia HR 2.83 (95% CrI 1.96 - 4.08) when compared to RAASi, however, it was not notice when compared to triple therapy HR 2.83 (95% CrI 0.83 - 9.62). All therapies reduced the risk of all-cause death as follows finerenone+RAASi (HR 0.88, 95% CrI 0.80 - 0.98), SGLT2i+RAASi HR 0.78 (95% CrI 0.66 - 0.91) and SGLT2i+finerenone+RAASi HR 0.69 (95% CrI 0.63 - 0.75). Conclusion: This NMA suggests that triple therapy with SGLT2i+finerenone+RAASi is superior in reducing cardiorenal events compared to single or dual therapy with a similar safety profile.