Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium–Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis
Diabetes Care 2022; online ahead of print doi: 10.2337/dc22-0294
In the FIDELITY analysis, finerenone reduced the risk of cardiovascular and kidney outcomes compared with placebo. Concomitant treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) did not modify the observed benefits.
FIDELITY pooled populations from the FIDELIO-DKD and FIGARO-DKD studies in order to examine the effect of finerenone and interaction with SGLT2i use on prespecified outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). In both trial, use of SGLT2i was permitted at baseline, as was initiation of SGLT2i at any time during the trial.
Effect of Canagliflozin on Total Cardiovascular Burden in Patients With Diabetes and Chronic Kidney Disease: A Post Hoc Analysis From the CREDENCE Trial
J Am Heart Assoc 2022;11:e025045 DOI: 10.1161/JAHA.121.025045
Cardiovascular disease is highly prevalent, and represents a major burden in patients with both T2D and CKD. In the CREDENCE trial, canagliflozin reduced the risk of first composite cardiovascular events; this post hoc analysis evaluated the effect on total (first and recurrent) events. During the trial, a total of 883 cardiovascular events occurred in 634 patients; 72% were first and 28% were subsequent events. Analysis showed canagliflozin reduced first and total cardiovascular events by 26% and 29%, respectively, with consistent results across patient subgroups and by baseline cardiovascular history.
These findings provide further support for the benefit of continuing canagliflozin therapy after an initial event to prevent recurrent CV events.
Effects of Canagliflozin Versus Finerenone on Cardiorenal Outcomes: Exploratory Post Hoc Analyses From FIDELIO-DKD Compared to Reported CREDENCE Results
Nephrol Dial Transplant 2022;37:1261-9 doi.org/10.1093/ndt/gfab336
This analysis highlights the pitfalls of direct comparisons between trials, since when key differences in design are considered, FIDELIO-DKD and CREDENCE demonstrate similar cardiorenal benefits. The authors conclude that both canagliflozin and finerenone are similarly effective in reducing the risk of cardiorenal outcomes.
Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using an UACR Endpoint study (CONFIDENCE)
Nephrol Dial Transplant 2022 Jun 14;gfac198. Online ahead of print. doi: 10.1093/ndt/gfac198.
CONFIDENCE is a new trial currently recruiting. The aim is to demonstrate that 6 months’ dual therapy with finerenone and empagliflozin is superior for reducing albuminuria versus either agent alone.
Despite available interventions, people with T2D remain at risk of chronic kidney disease, which puts them at further risk of kidney failure, CV morbidity, and all-cause mortality. There is therefore a need to slow or attenuate the progression of chronic kidney disease (CKD) and reduce CV morbidity and mortality in this population.
Finerenone and sodium-glucose cotransporter-2 inhibitors (SGLT2i) can both reduce kidney and CV risks, acting via both shared and distinct pathophysiological pathways. Results from post hoc subgroup analyses and a preclinical model suggest dual therapy may provide additive renoprotective effects than using either class alone.
Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER
Circulation 2022;145:575–85 doi: 10.1161/CIRCULATIONAHA.121.055459
In this analysis by Shaman et al., semaglutide and liraglutide offered kidney-protective effects in patients with type 2 diabetes, especially those with pre-existing chronic kidney disease.
Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy
Kidney Int Rep 2022;7:36–45 doi.org/10.1016/j.ekir.2021.10.008
Finerenone was associated with a 31% greater reduction in urine albumin:creatinine ratio (UACR) from baseline to Month 4 versus placebo. With similar reductions in UACR seen whether the patient was receiving SGLT2i at baseline or not.
Effects of Canagliflozin Versus Finerenone on Cardiorenal Outcomes: Exploratory Post-Hoc Analyses From FIDELIO-DKD Compared to Reported CREDENCE Results
Nephrol Dial Transplant 2021;gfab336 doi: 10.1093/ndt/gfab366
Finerenone and canagliflozin reduce cardiorenal risk in patients who are albuminuric. This exploratory post-hoc analyses by Agarwal et al. investigated how differences in trial design influenced observed treatment effects in the FIDELIO-DKD and CREDENCE studies.
N Engl J Med 2021;385:2252–63 doi: 10.1056/NEJMoa2110956
Finerenone has desirable effects on cardiorenal outcomes in patients with stage 3 or 4 chronic kidney disease (CKD), type 2 diabetes and severely elevated albuminuria. The outcomes of the use of finerenone are unclear in patients with type 2 diabetes and a wider range of CKD.