Combination therapy with an <scp>SGLT</scp>‐2 inhibitor and finerenone in <scp>DKD</scp>: Are we there yet?

Georgianos, Panagiotis I.; Eleftheriadis, Theodoros; Liakopoulos, Vassilios

doi:10.1111/eci.13864

Cited by 5 publications

(5 citation statements)

References 14 publications

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“…Nevertheless, it has been discussed that additional evidence from randomized trials may be needed to further substantiate findings and provide 'final' evidence. 40,41 However, the narrow CIs in the present analysis provide strong evidence in addition to that of previous analyses. This may be considered an overall robust set of data from which to conclude that the treatment effects of finerenone on kidney (and cardiovascular) benefits are largely independent of, and additive to, SGLT2 inhibitor and GLP-1RA treatment.…”

Section: Co-administration With Sglt2 Inhibitors and Glp-1rassupporting

confidence: 73%

“…They are also in line with preclinical data as well as clinical data generated for other MR antagonists, including finerenone, 37,38,39 in combination with an SGLT2 inhibitor. Nevertheless, it has been discussed that additional evidence from randomized trials may be needed to further substantiate findings and provide ‘final’ evidence 40,41 . However, the narrow CIs in the present analysis provide strong evidence in addition to that of previous analyses.…”

Section: Discussionmentioning

confidence: 42%

“…This may be considered an overall robust set of data from which to conclude that the treatment effects of finerenone on kidney (and cardiovascular) benefits are largely independent of, and additive to, SGLT2 inhibitor and GLP‐1RA treatment. New data may still provide additional insight, for example, on effects with simultaneous initiation of finerenone and an SGLT2 inhibitor 40 …”

Section: Discussionmentioning

confidence: 99%

“…New data may still provide additional insight, for example, on effects with simultaneous initiation of finerenone and an SGLT2 inhibitor. 40…”

Section: Co-administration With Sglt2 Inhibitors and Glp-1rasmentioning

confidence: 99%

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Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO‐DKD and FIDELIO‐DKD

Eissing,

Goulooze,

van den Berg

et al. 2023

Diabetes Obesity Metabolism

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AimsTo perform dose–exposure–response analyses to determine the effects of finerenone doses.Materials and MethodsTwo randomized, double‐blind, placebo‐controlled phase 3 trials enrolling 13 026 randomized participants with type 2 diabetes (T2D) from global sites, each with an estimated glomerular filtration rate (eGFR) of 25 to 90 mL/min/1.73 m2, a urine albumin‐creatinine ratio (UACR) of 30 to 5000 mg/g, and serum potassium ≤ 4.8 mmol/L were included. Interventions were titrated doses of finerenone 10 or 20 mg versus placebo on top of standard of care. The outcomes were trajectories of plasma finerenone and serum potassium concentrations, UACR, eGFR and kidney composite outcomes, assessed using nonlinear mixed‐effects population pharmacokinetic (PK)/pharmacodynamic (PD) and parametric time‐to‐event models.ResultsFor potassium, lower serum levels and lower rates of hyperkalaemia were associated with higher doses of finerenone 20 mg compared to 10 mg (p < 0.001). The PK/PD model analysis linked this observed inverse association to potassium‐guided dose titration. Simulations of a hypothetical trial with constant finerenone doses revealed a shallow but increasing exposure–potassium response relationship. Similarly, increasing finerenone exposures led to less than dose‐proportional increasing reductions in modelled UACR. Modelled UACR explained 95% of finerenone's treatment effect in slowing chronic eGFR decline. No UACR‐independent finerenone effects were identified. Neither sodium‐glucose cotransporter‐2 (SGLT2) inhibitor nor glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment significantly modified the effects of finerenone in reducing UACR and eGFR decline. Modelled eGFR explained 87% of finerenone's treatment effect on kidney outcomes. No eGFR‐independent effects were identified.ConclusionsThe analyses provide strong evidence for the effectiveness of finerenone dose titration in controlling serum potassium elevations. UACR and eGFR are predictive of kidney outcomes during finerenone treatment. Finerenone's kidney efficacy is independent of concomitant use of SGLT2 inhibitors and GLP‐1RAs.

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Section: Co-administration With Sglt2 Inhibitors and Glp-1rassupporting

confidence: 73%

Section: Discussionmentioning

confidence: 42%

Section: Discussionmentioning

confidence: 99%

“…New data may still provide additional insight, for example, on effects with simultaneous initiation of finerenone and an SGLT2 inhibitor. 40…”

Section: Co-administration With Sglt2 Inhibitors and Glp-1rasmentioning

confidence: 99%

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Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO‐DKD and FIDELIO‐DKD

Eissing,

Goulooze,

van den Berg

et al. 2023

Diabetes Obesity Metabolism

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“…In a preclinical model of hypertension-induced end-organ damage, the combined use of a SGLT-2 inhibitor and finerenone at low doses resulted in an over-additive reduction in albuminuria and in greater regression of cardiac and kidney fibrosis compared with the respective mono-therapies [47]. The research hypothesis for a synergistic effect on cardiorenal outcomes with the combination of a SGLT-2 inhibition and finerenone is currently under investigation in an ongoing phase 2 trial that is planning to recruit 807 patients with T2D, stage 2-3 CKD and severely increased albuminuria [48,49].…”

Section: Mineralocorticoid Receptorsmentioning

confidence: 99%

Albuminuria and cardiorenal risk

Georgianos¹,

Dounousi

Liakopoulos³

2023

Current Opinion in Cardiology

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Purpose of reviewThis article explores the prognostic association of albuminuria with the risk of adverse health outcomes and also provides an overview of novel guideline-directed therapies that confer cardiorenal protection in chronic kidney disease (CKD) patients with or without type 2 diabetes. Recent findingsAlthough the identification of CKD is based on the simultaneous assessment of estimated glomerular filtration rate and albuminuria, recent studies have shown that the regular screening rate for an increased urinary albumin-to-creatinine ratio is very low in daily clinical practice. Accordingly, a large proportion of high-risk patients with early-stage CKD remain unidentified, missing the opportunity to receive optimized treatment with novel agents that are effective in causing regression of albuminuria and in improving adverse cardiorenal outcomes.

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Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now

Georgianos,

Vaios,

Koufakis

et al. 2024

Drugs

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Combination therapy with an SGLT‐2 inhibitor and finerenone in DKD: Are we there yet?

Cited by 5 publications

References 14 publications

Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO‐DKD and FIDELIO‐DKD

Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO‐DKD and FIDELIO‐DKD

Albuminuria and cardiorenal risk

Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now

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