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.
Obesity and Effects of Dapagliflozin on Cardiovascular and Renal Outcomes in Patients With Type 2 Diabetes Mellitus in the DECLARE-TIMI 58 trial
Eur Heart J 2022;43:2958-67 doi.org/10.1093/eurheartj/ehab530
In the DECLARE-TIMI 58 trial, patients with type 2 diabetes and higher body weight were more likely to have hospitalisation for heart failure (HHF) and atrial fibrillation or flutter (AF/AFL).
Effect of Empagliflozin on Kidney Biochemical and Imaging Outcomes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure with Reduced Ejection Fraction (SUGAR-DM-HF)
Circulation 2022;146:364-7 DOI: 10.1161/CIRCULATIONAHA.122.059851
This study found that a reduction in kidney perfusion and congestion may be mechanisms by which sodium-glucose cotransporter-2 inhibitors (SGLT2i) affect kidney function in people with heart failure with reduced ejection fraction (HFrEF). The authors believe this is the first kidney MRI trial using SGLT2i in this patient group.
Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes
Circulation 2022; online ahead of print
In patients enrolled in EMPEROR-Preserved, empagliflozin significantly reduced the risk of heart failure (HF) outcomes irrespective of diabetes status.
Keywords:
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).
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.
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.
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.