Finerenone versus spironolactone in patients with chronic kidney disease and type 2 diabetes: a target trial emulation

Abstract

The comparative effectiveness of finerenone and spironolactone in chronic kidney disease (CKD) with type 2 diabetes (T2D) remains unclear. Here we show, using a target trial emulation on global real-world data from TriNetX, outcomes among 2268 propensity score-matched adults with CKD (eGFR 15-60 mL/min/1.73 m²) and T2D who initiated finerenone or spironolactone between July 2021 and September 2024. Over a median follow-up of 1.3 years, finerenone is associated with lower risks of major adverse cardiovascular events (adjust hazard ratio [aHR], 0.74; 95% CI, 0.58-0.94), major adverse kidney events (aHR, 0.47; 95% CI, 0.33-0.67), all-cause mortality (aHR, 0.31; 95% CI, 0.21-0.45), and hyperkalemia (17.2% vs. 26.4%; P < 0.001) compared with spironolactone. These findings suggest potential benefits of finerenone over spironolactone in reducing mortality and cardiorenal risk among patients with CKD and T2D.

Fig. 1. Study cohort construction and exclusion criteria.

^*CKD was defined by two eGFR values < 60 mL/min/1.73 m² (using the Modification of Diet in Renal Disease Study [MDRD] formula), separated by at least 90 days. ^†Strong CYP3A4 inhibitors, for example ketoconazole, clarithromycin, etc. CKD chronic kidney disease, CYP3A4 cytochrome P450 3A4, ESKD end stage kidney disease, ICH intracranial hemorrhage, MRA mineralocorticoid receptor antagonist, PSM propensity score matching.

Fig. 2. Cumulative incidence of study outcomes in patients with chronic kidney disease and type 2 diabetes.

A MACE. B MAKE. C All-cause mortality. Kaplan–Meier curves show estimated survival/event-free probabilities for each treatment group (centre), with shaded areas indicating 95% confidence intervals (error bands). The number at risk and the number of events at each time point are shown below each panel. Sample sizes for both finerenone and spironolactone groups are n = 1132, with each patient representing an independent biological replicate. P values were calculated using a two-sided log-rank test. Exact p values are provided where available; otherwise, p values are reported as <0.001 when below this threshold. No adjustments were made for multiple comparisons. Source data are provided as a Source data file. MACE major adverse cardiac events, MAKE major adverse kidney events.

Fig. 3. Adjusted hazard ratios for primary outcomes across prespecified subgroups.

Points represent the estimated hazard ratio (measure of centre) for each subgroup, and horizontal lines represent the corresponding 95% confidence intervals (error bars). Sample sizes for both finerenone and spironolactone groups are n = 1132, with each patient representing an independent biological replicate. P values for interaction were derived from likelihood‑ratio χ² tests comparing Cox models with versus without the treatment × subgroup interaction terms in the PS‑matched cohort. Exact p values are provided where available; otherwise, p values are reported as <0.001 when below this threshold. No adjustments were made for multiple comparisons. Source data are provided as a Source data file. eGFR estimated glomerular filtration rate, HbA1c glycated hemoglobin, HF heart failure, MACE major adverse cardiac events, MAKE major adverse kidney events, RAS renin-angiotensin system, SGLT2 sodium-glucose cotransporter-2, UPCR urine protein and creatinine ratio.