A Systematic Review and Meta-Analysis on the Efficacy and Safety of Finerenone Therapy in Patients with Cardiovascular and Chronic Kidney Diseases in Type 2 Diabetes Mellitus

Abstract

The purpose of this study is to assess the safety and efficacy of finerenone therapy in type 2 diabetes mellitus (T2DM) patients with cardiovascular and chronic renal diseases. This meta-analysis assesses the efficacy and safety of finerenone in the treatment of diabetic kidney disease (DKD). A comprehensive search of PubMed, Embase, and Google Scholar databases was performed to identify relevant randomized controlled trials (RCTs). To quantify the effects of finerenone, the analysis included the estimation of aggregated mean differences (MDs) and relative risks (RRs), as well as 95% confidence intervals (CIs). This meta-analysis included seven double-blind trials with patients suffering from chronic kidney disease (CKD) and T2D. Participants received finerenone or a placebo was assigned at random. The primary efficacy outcomes were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, kidney failure, a sustained 57% decrease in the estimated glomerular filtration rate from baseline over four weeks, or renal death. Among the 39,995 patients included in the analysis, finerenone treatment was associated with a lower risk of cardiovascular and renal-related mortality compared to placebo (RR = 0.86 (0.80, 0.93), p = 0.0002; I-squared statistic (I² ) = 0%) and (RR = 0.56 (0.17, 1.82), p = 0.34; I² = 0%). In addition, finerenone treatment was associated with a marginally reduced risk of serious adverse events (RR = 0.95 (0.92, 0.97), p = 0.0001; I² = 0%), although no significant difference in the overall risk of adverse events was observed between the two groups (RR = 1.00 (0.99, 1.01), p = 0.56; I² = 0%). This study's findings suggest that finerenone administration can reduce the risk of end-stage kidney disease, renal failure, cardiovascular mortality, and hospitalization. Patients with both T2DM and CKD are therefore advised to consider finerenone therapy.

Keywords: cardiovascular disease; chronic kidney disease; ckd; diabetes; finerenone; meta-analysis; non-steroidal mineralocorticoid receptor antagonist.

Figure 1. PRISMA flow diagram illustrating the search strategy and study selection process for the meta-analysis.

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Figure 2. Quality assessment of the included randomized controlled trials.

The trials of medium to high quality were identified using the Cochrane method for assessing randomized controlled trials (RCTs) [5,10,13-17].

Figure 3. Funnel plots for A) kidney failure, B) ESRD (end-stage renal disease).

RR (relative risk) was used as effect measures and SE (standard error) as a measure of precision. The funnel plots indicated no evidence of publication bias.

Figure 4. Funnel plots for A) sustained decrease to 15 mL/min/1.73 m2, B) sustained decrease of eGFR (estimated glomerular filtration rate) by >40% from baseline).

RR (relative risk) was used as effect measures and SE (standard error) as a measure of precision. The funnel plots indicated no evidence of publication bias.

Figure 5. Funnel plots for A) death from renal causes and B) cardiovascular-related mortality.

RR (relative risk) was used as effect measures and SE (standard error) as a measure of precision. The funnel plots indicated no evidence of publication bias.

Figure 6. Funnel plots for A) hospitalization for heart failure and B) nonfatal myocardial infarction.

RR (relative risk) was used as effect measures and SE (standard error) as a measure of precision. The funnel plots indicated no evidence of publication bias.

Figure 7. Funnel plot for nonfatal stroke.

RR (relative risk) was used as effect measures and SE (standard error) as a measure of precision. The funnel plots indicated no evidence of publication bias.

Figure 8. Forest plot for kidney failure.

RR: relative risk; CI: confidence interval; M-H: Mantel Hansel [5,10,14,15]

Figure 9. Forest plot for end-stage kidney disease.

RR: relative risk; CI: confidence interval; M-H: Mantel Hansel [5,10,14,15]

Figure 10. Forest plot of sustained decrease to 15 mL/min/1.73 m2.

RR: relative risk; CI: confidence interval; M-H: Mantel Hansel [5,10,14,15]

Figure 11. Forest plot showing sustained decrease of eGFR of >40% from baseline.

eGFR: estimated glomerular filtration rate; RR: relative risk; CI: confidence interval; M-H: Mantel-Hansel [5,10,14]

Figure 12. Forest plot showing death from renal causes.

RR: relative risk; CI: confidence interval; M-H: Mantel-Hansel [5,10,14]

Figure 13. Forest plot showing death from cardiovascular causes.

RR: relative risk; CI: confidence interval; M-H: Mantel-Hansel [5,10,14-16]

Figure 14. Forest plot showing the number of patients hospitalized for heart failure.

RR: relative risk; CI: confidence interval; M-H: Mantel-Hansel [5,10,14-16]

Figure 15. Forest plot showing the rate of nonfatal MI (myocardial infarction).

RR: relative risk; CI: confidence interval; M-H: Mantel-Hansel [5,10,14,15]

Figure 16. Forest plot showing the rate of nonfatal stroke.

RR: relative risk; CI: confidence interval; M-H: Mantel-Hansel [5,10,14,15]