Physicians' Academy for Cardiovascular Education

Cardiorenal benefits of nonsteroidal MRA not modified by HbA1c levels, HbA1c variability, diabetes duration, or insulin use

Effects of finerenone in persons with CKD and T2D are independent of HbA1c at baseline, HbA1c variability, diabetes duration and insulin use at baseline

Literature - McGill JB, Agarwal R, Anker SD, et al - Diabetes Obes Metab. 2023 Feb 1 [Online ahead of print]. doi: 10.1111/dom.14999

Introduction and methods


In patients with T2DM, both the level and the variability of HbA1c are associated with an increased risk of adverse cardiorenal outcomes and all-cause mortality [1-4]. In addition, T2DM duration is independently associated with an increased risk of microvascular and macrovascular complications [5-7]. Moreover, insulin-treated T2DM patients tend to have higher rates of CV death and HF hospitalization because of the high level of comorbidities [8].

Previously, the selective, nonsteroidal MRA finerenone was shown to reduce the risk of adverse cardiorenal outcomes in patients with both T2DM and CKD compared with placebo, as shown by the complementary FIDELIO-DKD and FIGARO-DKD trials and their pooled FIDELITY analysis [9-12]. As excessive aldosterone and associated MR activation lead to the development of T2DM [13,14], finerenone may decrease the progression of this disease.

Aim of the study

Using the FIDELITY dataset, the authors investigated the effect of finerenone on cardiorenal outcomes and diabetes progression and the safety of this agent in patients with T2DM and CKD, stratified by baseline HbA1c levels, continuous HbA1c variability in the first year of treatment, diabetes duration at baseline, and baseline insulin use.


This was a post-hoc analysis of the prespecified pooled FIDELITY dataset, which combined individual patient-level data from 2 multicenter, double-blind, placebo-controlled, phase 3 RCTs (FIDELIO-DKD and FIGARO-DKD). In these trials, a total of 13,026 patients with T2DM and CKD were randomized to finerenone 20 mg (10 mg if eGFR <60 mL/min per 1.73 m2) or placebo. Median follow-up duration of the pooled dataset was 3.0 years (IQR: 2.3–3.8).


Efficacy endpoints were a composite CV outcome (consisting of CV death, nonfatal MI, non-fatal stroke, or HF hospitalization); a composite kidney outcome (kidney failure, sustained eGFR decline ≥57% from baseline for ≥4 weeks, or renal death); and a composite outcome of diabetes progression (new insulin initiation, increase in number of antidiabetic medication classes, HbA1c increase of 1.0% from baseline, new diagnosis of diabetic ketoacidosis, or uncontrolled diabetes).

To assess safety, the incidences of adverse events and treatment-emergent hyperkalemia and hypoglycemia were evaluated.

Main results

Composite CV outcome

Composite kidney outcome

Composite diabetes progression outcome

Safety outcomes


In this post-hoc analysis of the prespecified pooled FIDELITY dataset, the cardiorenal benefits of finerenone over placebo in T2DM patients with CKD were not modified by baseline HbA1c levels, HbA1c variability in the first year, baseline diabetes duration, or baseline insulin use. Finerenone had no effect on diabetes progression. Of note, HbA1c variability was associated with increased risk of cardiorenal outcomes. Finerenone was well-tolerated across subgroups.


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Find this article online at Diabetes Obes Metab.

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