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Aim: To assess the effect of empagliflozin on patients with comorbid heart failure (HF) and diabetes with or without baseline insulin, and to study the impact of empagliflozin on insulin requirements over time. Materials and Methods: We performed a post‐hoc analysis of pooled patient‐level data from two cardiovascular outcomes trials of empagliflozin in HF (EMPEROR‐Reduced and EMPEROR‐Preserved trials). We undertook a subgroup analysis stratified by baseline insulin use, including all patients with diabetes. The studied endpoints included the primary composite endpoint of first hospitalization for HF or cardiovascular death, rate of decline of estimated glomerular filtration rate, composite renal outcome and rates of sustained insulin initiation. Results: Among 4794 patients with diabetes, 1333 (658 in empagliflozin, 675 in placebo) were using insulin at baseline. The treatment effect of empagliflozin on the primary endpoint was consistent irrespective of insulin use [no insulin, hazard ratio 0.74, 95% confidence interval (CI) 0.63‐0.86; using insulin, hazard ratio 0.81, 95% CI 0.66‐1.00, pinteraction =.49], as was the effect on the rate of decline of the estimated glomerular filtration rate (pinteraction =.75). There was no effect of empagliflozin on the composite renal outcome in patients using or not using insulin (pinteraction =.30). Among patients not using insulin at baseline, those randomized to empagliflozin initiated insulin less frequently throughout the follow‐up period compared with those receiving placebo (2.6% vs. 3.8%, odds ratio 0.66, 95% CI 0.50‐0.88). Conclusions: Empagliflozin exerts a consistent benefit on cardiovascular outcomes and renal function decline, irrespective of baseline insulin use, and reduces the need for sustained insulin initiation in patients with HF and diabetes. [ABSTRACT FROM AUTHOR]

Aim: Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis. Materials and Methods: Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis‐4 (FIB‐4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma‐glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke or hospitalization for heart failure. Results: ALT, aspartate aminotransferase and gamma‐glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB‐4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB‐4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction =.01,.13 and.03, respectively). Conclusions: Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB‐4 scores who were at high risk of developing cardiovascular complications. [ABSTRACT FROM AUTHOR]

Aim: To assess the effect of finerenone on the risk of cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes, with and without obesity. Materials and methods: A post hoc analysis of the prespecified pooled FIDELITY dataset assessed the association between waist circumference (WC), composite cardiovascular and kidney outcomes, and the effects of finerenone. Participants were stratified by WC risk groups (representing visceral obesity) as low‐risk or high–very high‐risk (H‐/VH‐risk). Results: Of 12 986 patients analysed, 90.8% occupied the H‐/VH‐risk WC group. Incidence of the composite cardiovascular outcome was similar between finerenone and placebo in the low‐risk WC group (hazard ratio [HR] 1.03; 95% confidence interval [CI], 0.72‐1.47); finerenone reduced the risk in the H‐/VH‐risk WC group (HR 0.85; 95% CI, 0.77‐0.93). For the kidney outcome, the risk was similar in the low‐risk WC group (HR 0.98; 95% CI, 0.66‐1.46) and reduced within the H‐/VH‐risk WC group (HR 0.75; 95% CI, 0.65‐0.87) with finerenone versus placebo. There was no significant heterogeneity between the low‐risk and H‐/VH‐risk WC groups for cardiovascular and kidney composite outcomes (P interaction =.26 and.34, respectively). The apparent greater benefit of finerenone on cardiorenal outcomes but lack of significant heterogeneity observed in H‐/VH‐risk WC patients may be because of the small size of the low‐risk group. Adverse events were consistent across WC groups. Conclusion: In FIDELITY, benefits of finerenone in lowering the risk of cardiovascular and kidney outcomes were not significantly modified by patient obesity. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of finerenone by baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use on cardiorenal outcomes and diabetes progression. Materials and Methods: Composite efficacy outcomes included cardiovascular (cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke or hospitalization for heart failure), kidney (kidney failure, sustained ≥ 57% estimated glomerular filtration rate decline or renal death) and diabetes progression (new insulin initiation, increase in antidiabetic medication, 1.0% increase in HbA1c from baseline, new diabetic ketoacidosis diagnosis or uncontrolled diabetes). Results: In 13 026 participants, risk reductions in the cardiovascular and kidney composite outcomes with finerenone versus placebo were consistent across HbA1c quartiles (P interaction.52 and.09, respectively), HbA1c variability (P interaction.48 and.10), diabetes duration (P interaction.12 and.75) and insulin use (P interaction.16 and.52). HbA1c variability in the first year of treatment was associated with a higher risk of cardiovascular and kidney events (hazard ratio [HR] 1.20; 95% confidence interval [CI] 1.07‐1.35; P =.0016 and HR 1.36; 95% CI 1.21‐1.52; P <.0001, respectively). There was no effect on diabetes progression with finerenone or placebo (HR 1.00; 95% CI 0.95‐1.04). Finerenone was well‐tolerated across subgroups; discontinuation and hospitalization because of hyperkalaemia were low. Conclusions: Finerenone efficacy was not modified by baseline HbA1c, HbA1c variability, diabetes duration or baseline insulin use. Greater HbA1c variability appeared to be associated with an increased risk of cardiorenal outcomes. [ABSTRACT FROM AUTHOR]

Aims: To explore the modifying effect of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use on outcomes with finerenone across a wide spectrum of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the pooled analysis of FIDELIO‐DKD and FIGARO‐DKD. Materials and methods: Patients with T2D and CKD treated with optimized renin‐angiotensin system blockade were randomized to finerenone or placebo. Effects of finerenone on a cardiovascular composite outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and a kidney composite outcome (kidney failure, sustained ≥57% estimated glomerular filtration rate [eGFR] decline, or renal death), change in urine albumin‐to‐creatinine ratio (UACR), and safety were analysed by GLP‐1RA use. Results: Of 13 026 patients, 944 (7.2%) used GLP‐1RAs at baseline. Finerenone reduced the risk of the cardiovascular composite outcome (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.52–1.11 with GLP‐1RA; HR 0.87, 95% CI 0.79–0.96 without GLP‐1RA; P‐interaction = 0.63) and the kidney composite outcome (HR 0.82, 95% CI 0.45–1.48 with GLP‐1RA; HR 0.77, 95% CI 0.67–0.89 without GLP‐1RA; P‐interaction = 0.79) irrespective of baseline GLP‐1RA use. Reduction in UACR with finerenone at Month 4 was –38% in patients with baseline GLP‐1RA use compared with –31% in those without GLP‐1RA use (P‐interaction = 0.03). Overall safety and incidence of hyperkalaemia were similar, irrespective of GLP‐1RA use. Conclusions: The cardiorenal benefits of finerenone on composite cardiovascular and kidney outcomes and UACR reduction in patients with CKD and T2D appear to be maintained, regardless of GLP‐1RA use. Subsequent studies are needed to investigate any potential benefit of this combination. [ABSTRACT FROM AUTHOR]

Aims: Finerenone significantly reduced the risk of kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease and type 2 diabetes in the FIDELIO‐DKD trial (NCT02540993). This exploratory subgroup analysis investigates the effect of glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use on the treatment effect of finerenone. Materials and Methods: Patients with type 2 diabetes, urine albumin‐to‐creatinine ratio (UACR) 30‐5000 mg/g and estimated glomerular filtration rate 25‐<75 ml/min per 1.73 m2 receiving optimized renin‐angiotensin system blockade were randomized to finerenone or placebo. Results: Of the 5674 patients analysed, overall, 394 (6.9%) received GLP‐1RAs at baseline. A reduction in UACR with finerenone was observed with or without baseline GLP‐1RA use; ratio of least‐squares means 0.63 (95% confidence interval 0.56, 0.70) with GLP‐1RA use and 0.69 (95% confidence interval 0.67, 0.72) without GLP‐1RA use (p value for interaction.20). Finerenone also significantly reduced the primary kidney (time to kidney failure, sustained decrease in estimated glomerular filtration rate ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, non‐fatal myocardial infarction, non‐fatal stroke, or hospitalization for heart failure) versus placebo, with no clear difference because of GLP‐1RA use at baseline (p value for interaction.15 and.51 respectively) or any time during the trial. The safety profile of finerenone was similar between subgroups. Conclusions: This exploratory subgroup analysis suggests that finerenone reduces UACR in patients with or without GLP‐1RA use at baseline, and the effects on kidney and CV outcomes are consistent irrespective of GLP‐1RA use. [ABSTRACT FROM AUTHOR]

The cover image is based on the Original Article Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis by Nikolaos Perakakis MD et al., https://doi.org/10.1111/dom.15305. [ABSTRACT FROM AUTHOR]

The outside back cover image is based on the Original Article I The impact of obesity on cardiovascular and kidney outcomes in patients with chronic kidney disease and type 2 diabetes treated with finerenone: Post hoc analysis of the FIDELITY study i by Peter Rossing MD et al., https://doi.org/10.1111/dom.15197. [Extracted from the article]

The outside front cover image is based on the Original Article I Finerenone in patients across the spectrum of chronic kidney disease and type 2 diabetes by glucagon-like peptide-1 receptor agonist use i by Peter Rossing MD et al., https://doi.org/10.1111/dom.14883. [Extracted from the article]