Efficacy and Safety of Finerenone in Type 2 Diabetes: A Pooled Analysis of Trials ofHeart Failure and Chronic Kidney Disease

Objective: To evaluate the efficacy and safety of finerenone, a non-steroidal mineralocorticoid receptor antagonist, in individuals with type 2 diabetes (T2D) and either chronic kidney disease (CKD) or heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

Research Design and Methods: In this prespecified participant-level pooled analysis of all phase III clinical trials evaluating finerenone versus placebo conducted to date (FINE-HEART), the safety and efficacy of finerenone was evaluated among participants with a history of T2D. Treatment effects on the primary outcome of cardiovascular death and other secondary outcomes were evaluated according to baseline glycated hemoglobin (HbA_1c) and glucose-lowering therapy (GLT) regimen using stratified Cox proportional hazards models.

Results: Of 18,991 FINE-HEART participants, 15,365 (80.9%) had T2D and available HbA_1c at baseline (mean age, 66±10 years; 32% women; mean HbA_1c, 7.6±1.4%). The most common GLT regimens were insulin alone (n=2,652), insulin and metformin (n=2,005), metformin alone (n=1,616), metformin and sulfonylurea (n=1,039), and “other” (n=8,117; including SGLT2i and GLP-1RA). Over a median follow-up of 2.9 years, treatment effects of finerenone vs. placebo on cardiovascular death were consistent across baseline HbA_1c (P_interaction=0.75) and GLT regimen (P_interaction=0.46). Finerenone consistently reduced the kidney composite outcome, HF hospitalization, major adverse cardiovascular events, and all-cause mortality, irrespective of baseline HbA_1c and GLT regimen. Treatment effects of finerenone were also consistent across number of background GLTs and irrespective of concomitant treatment with a SGLT2i or GLP-1RA.

Conclusions: Finerenone consistently reduced morbidity and mortality in individuals with T2D across a broad range of glycemia and glucose-lowering regimens.