Publications
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Zibotentan in Combination with Dapagliflozin Compared with Dapagliflozin in Patients with Chronic Kidney Disease (ZENITH-CKD): a Multicentre, Randomised, Active-controlled, Phase 2b, Clinical Trial
Lancet. 2023; online ahead of print DOI: 10.1016/S0140-6736(23)02230-4
The risk of kidney failure persists in many patients with CKD, even when receiving optimal treatment including SGLT2i. Increased expression of endothelin-1 may contribute to CKD progression through several pathophysiological effects; however, high doses of non-selective endothelin receptor antagonists (ERAs) have been linked with fluid retention.
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Decline in Estimated Glomerular Filtration Rate After Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial
JAMA Cardiol. 2023; online ahead of print DOI: 10.1001/jamacardio.2023.4664
An initial decline in eGFR often occurs after initiating a SGLT2i and has been observed in patients with diabetes, CKD and HF. A prespecified analysis of DELIVER evaluated the magnitude and frequency of an initial decline in eGFR (within the first month) and its association with CV and renal outcomes in 5,788 patients with HFpEF or HFmrEF.
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Glomerular and Tubular Effects of Dapagliflozin, Eplerenone and their Combination in Patients with Chronic Kidney Disease: A Post-hoc Analysis of the ROTATE-3 Study
Diabetes Obes Metab. 2023; online ahead of print DOI: 10.1111/dom.15346
The ROTATE-3 cross-over trial in 46 adults with CKD and urinary albumin excretion ≥100 mg/24 h showed that dapagliflozin combined with eplerenone led to robust additive reductions in albuminuria compared with either agent alone. This post-hoc analysis aimed to characterise the effects of dapagliflozin, eplerenone and the combination on markers of glomerular and tubular function to better understand the mechanisms responsible for albuminuria lowering.
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Efficacy of Finerenone in Patients with Type 2 Diabetes, Chronic Kidney Disease and Altered Markers of Liver Steatosis and Fibrosis: A FIDELITY Subgroup Analysis
Diabetes Obes Metab. 2023; online ahead of print DOI: 10.1111/dom.15305
This post hoc subgroup analysis from FIDELITY investigated the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with CKD and T2D, stratified by their risk of liver steatosis, inflammation and fibrosis.
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Albuminuria-Lowering Effect of Adding Semaglutide on Top of Empagliflozin in Individuals with Type 2 Diabetes: A Randomized and Placebo-Controlled Study
Diabetes Obes Metab. 2023; online ahead of print DOI: 10.1111/dom.15287
The proposed different mechanisms of SGLT2i and GLP-1RAs indicate that combination therapy may have additive or synergistic effects on the kidneys. This placebo-controlled, double-blind, parallel-group study investigated the effect on albuminuria of adding semaglutide to ongoing treatment with empagliflozin compared with empagliflozin alone in 60 individuals with T2D and albuminuria.
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Short-Term Costs in Patients with Chronic Kidney Disease Treated with Dapagliflozin: a Retrospective Cohort Study
Expert Rev Pharmacoecon Outcomes Res. 2023; online ahead of print DOI: 10.1080/14737167.2023.2237679
Analyses have found that dapagliflozin is cost-effective in the long term in patients with non-diabetic CKD and in patients with CKD with or without T2D. The slowing of eGFR decline and the early reduction in HF hospitalisation seen with dapagliflozin suggest that there is potential for short-term cost benefits in patients with CKD; however, there is a lack of real-world evidence. This retrospective observational cohort study described the impact of dapagliflozin on short-term medical costs in propensity matched patients with stage 3 CKD.
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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
Diabetes Obes Metab. 2023 doi Epub ahead of print : 10.1111/dom.15197
Patients with obesity may benefit more from treatment with mineralocorticoid receptor antagonists given their higher levels of circulating aldosterone and therefore potentially higher levels of MRs in visceral fat. The aim of this analysis was 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.
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Safety of Sodium-Glucose Cotransporter 2 Inhibitors in Elderly Patients with Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials
Diabetes Obes Metab 2023 DOI 10.1111/dom.15193
SGLT2is are effective in preventing adverse outcomes of heart failure and chronic kidney disease, which are highly prevalent in the elderly. While SGLT2is are generally well tolerated, elderly patients may be more susceptible to developing AEs reported with this class of drug, such as infections, fracture, and AKI. Clinical experience with SGLT2is in the elderly and very elderly is limited.
Mineralocorticoid Receptor Antagonist Use in Chronic Kidney Disease with Type 2 Diabetes: A Clinical Practice Document by the European Renal Best Practice (ERBP) Board of the European Renal Association (ERA)
Clin Kidney J. 2023;16:1885–1907
Patients with CKD and T2D are at high risk of both developing kidney failure and of CV events. With RAS blockers, residual risk of CKD progression remains high and no significant reduction in CV events and mortality has been seen in major studies in patients with CKD and T2D. Steroidal MRAs have been shown to reduce albuminuria in individuals on RAS monotherapy, but widespread clinical use is limited by the risk of hyperkalaemia and the absence of trials with hard renal outcomes. In recent years, non-steroidal MRAs have received increasing interest due to their better pharmacological profile, particularly finerenone, which effectively reduced CKD progression and CV outcomes in participants with T2D in Phase 3 trials.
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Effects of Dapagliflozin on Hospitalisations in People with Type 2 Diabetes: Post-hoc Analyses of the DECLARE-TIMI 58 Trial
Lancet Diabetes Endocrinol. 2023;11:233–241 DOI: 10.1016/S2213-8587(23)00009-8
In patients with T2D at high risk of CV or kidney disease, SGLT2is consistently reduce the risk of HF hospitalisations. Less is known about their effects on hospitalisation from any cause, especially in patients with T2D without ASCVD, which includes most of the global population with T2D. Post hoc analyses of DECLARE-TIMI 58 assessed the effect of dapagliflozin on the risks of hospitalisations for any cause and for specific causes in patients with T2D with and without ASCVD.