MAJOR ADVERSE EVENTS WITH THE USE OF FINERENONE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A META-ANALYSIS OF CARDIOVASCULAR OUTCOME TRIALS

Abstract

Objective: Type 2 diabetes mellitus (T2DM) is recognized as the main cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, carrying enormous human and financial costs. Mineralocorticoid receptor antagonists (MRAs) have been shown to decrease proteinuria and albuminuria, posing a favorable effect against the progression of CKD. Recently, we welcomed the publication of two large randomized controlled trials (RCTs), namely FIGARO-DKD and FIDELIO-DKD, addressing the cardio-renal efficacy of finerenone, a newer MRA, in patients with T2DM. Herein we sought to assess major adverse events with the use of finerenone in patients with T2DM. Design and method: We pooled data from the two relevant, published RCTs with finerenone in patients with T2DM, to provide pooled effect estimates for its cardio-renal efficacy and safety. We utilized data from published reports, also searching relevant supplementary appendices for any missing data. We assessed the following safety outcomes: acute kidney injury (AKI), hospitalization due to AKI, hyperkalemia, hospitalization due to hyperkalemia, all-cause death, hospitalization for any cause Results: We demonstrated that finerenone increased the risk for hyperkalemia by two times compared to placebo (RR = 2.03, 95% CI; 1.82–2.26, I2 = 0%, p < 0.00001), while it also significantly increased the risk for hospitalization due to hyperkalemia (RR = 5.86, 95% CI; 2.99 – 11.47, I2 = 0%, p < 0.00001). We have also documented that finerenone did not significantly affect the risk for development of AKI (p = 0.94) or hospitalization in the context of AKI (p = 0.92). In addition, finerenone resulted in a marginally non-significant reduction in the risk for all-cause death, equal to 10% (p = 0.05). Conclusions: Finerenone appears to provide significant cardiovascular and renal benefits for patients with T2DM. However, extra caution is required, since hyperkalemia appears to be the most important side effect with the use of finerenone, representing also the main cause of hospitalization due to a drug side effect. Large-scale use of potassium-binding drugs, such as patiromer or zirconium, as adjunct to finerenone might be a reasonable treatment combination in high-risk patients for hyperkalemia.