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.
Empagliflozin and Serum Potassium in Heart Failure: An Analysis From Emperor-Pooled
Eur Heart J 2022; online ahead of print DOI: 10.1093/eurheartj/ehac306
In this pooled analysis, empagliflozin reduced the incidence of hyperkalaemia without significant increase in hypokalaemia.
Potassium is essential for normal cellular function, but severe potassium abnormalities can lead to cardiac arrhythmias and death. Hyperkalaemia frequently leads to interruption and discontinuation of neurohormonal antagonists, which may worsen the prognosis for people with heart failure (HF).
Efficacy of Subcutaneous Semaglutide Compared to Placebo For Weight Loss in Obese, Non-diabetic Adults: A Systematic Review & Meta-Analysis
Int J Clin Pharm 2022; online ahead of print DOI: 10.1007/s11096-022-01428-1
This systematic review and meta-analysis validates the clinical efficacy of semaglutide for the treatment of obesity in adults without T2D. There is substantial evidence for clinicians to consider modification to their management obese population.
Research of the effect of semaglutide on weight loss has largely focused on T2D, and no meta-analyses in non-diabetic individuals have been conducted to date.
Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin: A Cohort Study
Ann Intern Med 2022; doi:10.7326/M21-4012
This cohort study found that those initiating a SGLT2i as their first-line treatment for T2D showed a similar risk for a composite outcome of MI, stroke, and mortality – and lower risk for a composite of hospitalisation for heart failure (HHF) and mortality. Compared with those receiving metformin as their first-line treatment, the SGLT2i safety profile was similar, except for an increased risk of genital infections.
Prognostic Implications of N-terminal Pro-B Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved
JACC Heart Fail 2022 doi:S2213-1779(22)00302-X
This planned analysis from EMPEROR-Preserved provides strong evidence for both N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) as important disease markers and prognostic indicators in people with heart failure with preserved ejection fraction (HFpEF).
Evaluation and management of individuals with HFpEF can be challenging. NT-proBNP and hs-cTnT are biomarkers with well-established prognostic role across the range of ejection fraction in heart failure. As such, it is possible that patient baseline values could be used to identify those suitable for treatment. However, ambiguity has led to confusion about pharmacologic management, and the role of biomarkers.
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.
Randomized Controlled Trial of the Hemodynamic Effects of Empagliflozin in Patients With Type 2 Diabetes at High Cardiovascular Risk: The SIMPLE Trial
Diabetes 2022;71:812–20 doi.org/10.2337/db21-0721
In this analysis of data from the SIMPLE trial, empagliflozin did not reduce left heart filling pressure more than placebo at submaximal exercise in patients with T2D at high CV risk. However, it was observed that empagliflozin reduced pulmonary capillary wedge pressure (PCWP) at a magnitude of clinical significance in patients at rest. The findings suggest cardiac benefits beyond the diuretic effect of sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment and could explain a significant part of the CV benefits observed in clinical trials.
Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure – Results From the EMPULSE Trial
Circulation 2022; online ahead of print doi:10.1161/CIRCULATIONAHA.122.059725
This post hoc and prespecified analysis of the EMPULSE trial found that initiation of empagliflozin in patients hospitalised for acute heart failure (AHF) produced clinical benefit regardless of the degree of symptomatic impairment at baseline. Empagliflozin also improved symptoms, physical limitations, and quality of life – with benefits seen as early as 15 days and maintained through 90 days.
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.