Publications
Stay up to date with our literature reviews which are curated by experts to feature the most important publications released each month. Explore our publications for access to concise summary slides for your own use.
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.
Dose–Exposure–Response Analysis of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone on UACR and eGFR: An Analysis from FIDELIO‑DKD
Clin Pharmacokinet 2022; Ahead of print doi: 10.1007/s40262-022-01124-3
The results of this model-based analysis quantified the dose–exposure–response relationship for urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Overall, the relationship between finerenone exposure and UACR and eGFR effects was not modified by sodium-glucose co-transporter-2 inhibitor (SGLT2i) use and demonstrated independent and additive effects.
Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients With Chronic Kidney Disease: A Randomized Cross-Over Clinical Trial
J Am Soc Nephrol 2022; ahead of print doi:10.1681/ASN.2022020207
This trial demonstrates that the albuminuria-lowering effects of dapagliflozin and eplerenone alone are additive when used in combination. A larger trial in this population is required to confirm long-term efficacy and safety of combined sodium-glucose co-transporter-2 inhibitor (SGLT2i) and mineralocorticoid receptor antagonist (MRA) treatment, but this may support the idea that these classes have complementary nephroprotective effects.
Initial Decline (“Dip”) in Estimated Glomerular Filtration Rate Following Initiation of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: Insights From DAPA-HF
Circulation 2022; Online ahead of print doi: 10.1161/CIRCULATIONAHA.121.058910
The results of this subgroup analysis from DAPA-HF show that – although estimated glomerular filtration rate (eGFR) decline is generally associated with poorer prognosis in most situations – an initial dip with a sodium-glucose co-transporter-2 inhibitor (SGLT2i) may be associated with slower rate of decline in kidney function.
Empagliflozin and Incidence of Events Consistent With Acute Kidney Injury: Pooled Safety Analysis in >15,000 Individuals
Diabetes Obes Metab 2022;doi:10.1111/dom.14694 Ahead of print
This comprehensive analysis indicates that empagliflozin is not associated with increased risk of acute kidney injury or acute kidney failure compared with placebo treatment.
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 patients with CKD and T2D with and without heart failure: A prespecified subgroup analysis of the FIDELIO-DKD trial
PMID: 35239204 DOI: 10.1002/ejhf.2469
This subgroup analysis of the FIDELIO-DKD trial discovered that finerenone improved cardiorenal outcome in patients with chronic kidney disease and type 2 diabetes.
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.
Dapagliflozin and New-Onset Type 2 Diabetes in Patients With Chronic Kidney Disease Or Heart Failure: Pooled Analysis of the DAPA-CKD and DAPA-HF Trials
Lancet Diabetes Endocrinol 2022;10:24–34 doi.org/10.1016/
Chronic kidney disease and heart failure are insulin resistant states associated with high incidence rates of diabetes. Rossing et al. carried out a two Phase 3, randomised, double-blind, placebo-controlled trials assessed the effect of dapagliflozin on new-onset type 2 diabetes, in a pooled analysis of data from 6,608 individuals.