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.
Benefits and Harms of Drug Treatment for Type 2 Diabetes: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials
BMJ 2023;381:e074068 DOI 10.1136/bmj-2022-074068
Keeping abreast of the rising volume of randomized trials in adults with type 2 diabetes presents a formidable task. Recent randomized trials have shown cardiovascular and kidney advantages with finerenone, an innovative non-steroidal mineralocorticoid receptor antagonist, and weight loss with tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GLP-1) receptor agonist.
Outcomes with Finerenone in Participants with Stage 4 CKD and Type 2 Diabetes: A FIDELITY Subgroup Analysis
Clin J Am Soc Nephrol. 2023; online ahead of print DOI: 10.2215/CJN.0000000000000149
Patients with stage 4 CKD and T2D have limited treatment options to reduce their persistent CV and kidney risk. This post hoc analysis of the FIDELITY database evaluated the effect of finerenone vs placebo in 890 patients with stage 4 CKD and T2D.
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Effects of Finerenone in Persons with CKD and T2D are Independent of HbA1c at Baseline, HbA1c Variability, Diabetes Duration and Insulin Use at Baseline
Diabetes Obes Metab. 2023; online ahead of print DOI: 10.1111/dom.14999
Given the role of HbA1c, diabetes duration and insulin use in determining morbidity and mortality of CKD in T2D, it is important to investigate whether these factors modify the efficacy and safety of therapies that mitigate the cardiorenal impact of CKD in T2D. This post hoc analysis of the FIDELITY database evaluated the effect of finerenone by baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use on cardiorenal outcomes and diabetes progression.
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Effect of Finerenone on Ambulatory Blood Pressure in Chronic Kidney Disease in Type 2 Diabetes
J Hypertens. 2023;41:295–302 DOI: 10.1097/HJH.0000000000003330
It has been postulated that the effects of finerenone on cardiorenal outcomes may be mediated primarily via non-haemodynamic pathways, but office BP measurements are insufficient to fully assess haemodynamic effects. A substudy of the ARTS-DN phase IIb trial was conducted to obtain further insights into the mechanism of action of finerenone by analysing 24-h ambulatory BP in patients with CKD and T2D.
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Finerenone efficacy in patients with chronic kidney disease, type 2 diabetes and atherosclerotic cardiovascular disease
Eur Heart J Cardiovasc Pharmacother. 2022; online ahead of print DOI: 10.1093/ehjcvp/pvac054
Finerenone reduced the risk of CV and kidney outcomes consistently across the spectrum of CKD in patients with T2D, irrespective of prevalent ASCVD.
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.
Empagliflozin and Incidence of Events Consistent With Acute Kidney Injury: Pooled Safety Analysis in More Than 15,000 Individuals
Diabetes Obes Metab 2022;24:1390-3 doi: 10.1111/dom.14694
In this pooled analysis of patients from the global empagliflozin trial programme, the risk of acute kidney injury (AKI) and acute kidney disease (AKD) with empagliflozin was comparable with placebo. This comprehensive analysis indicates that empagliflozin is not associated with an increased risk of acute kidney failure compared with placebo treatment.
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.