Study: Empagliflozin Can Slow Progression of Chronic Kidney Disease to Kidney Failure

The sodium–glucose cotransporter 2 (SGLT2) inhibitor empagliflozin reduced the progression of chronic kidney disease (CKD) in patients at risk for disease progression, according to data from the EMPA-KIDNEY study published in the New England Journal of Medicine.

“Empagliflozin treatment led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo,” the researchers wrote the analysis.

The study’s primary outcome was CKD progression (end-stage kidney disease), sustained low estimated glomerular filtration rate (eGFR) below 10 ml per minute per 1.73 m2 of body-surface area, an eGFR lower by 40% or more from baseline, or death from renal or cardiovascular causes.

CKD is a progressive disease and patients have severe symptoms such, as low eGFR and high levels of albuminuria that can progress the disease to kidney failure. A favorable outcome would be slowing CKD progression by avoiding dialysis and avoiding kidney transplant, which may lead to cardiovascular morbidity or mortality.

SGLT2 inhibitors have been found to reduce the risk of kidney failure in patients with increased albuminuria and diabetic kidney disease; however, the effects of the SGLT2 inhibitor empagliflozin were not fully understood, according to the study.

EMPA-KIDNEY was an international, randomized, parallel-group, double-blind, placebo-controlled, clinical trial that evaluated the safety and efficacy of empagliflozin for progressive kidney disease and cardiovascular disease (CVD) between February 2019 and April 2021. The study included 6609 randomized patients broadly representative of the CKD population at risk for disease progression, who were assigned either once daily empagliflozin at 10 mg or placebo.

Among patients with various GFRs, albuminuria levels, and other causes related to CKD, empagliflozin decreased the likelihood of disease progression or death from CVD-related causes by 28% compared to the placebo. Risk of any-cause hospitalization was also 14% lower in the empagliflozin arm compared to the placebo arm.

Additionally, death from renal or cardiovascular causes occurred less in the empagliflozin arm at 13.1%. Deaths occurred at a rate of 16.9% in the placebo group.

Empagliflozin had favorable results on GFR in all subgroups compared to placebo, including patients with diabetes and patients with a low urinary albumin-to-creatinine ratio.

“The benefits of empagliflozin treatment were consistent among patients with or without diabetes and regardless of the eGFR at randomization,” the study authors wrote.

Past and present studies found that SGLT2 inhibitors can lower the risk of death from cardiovascular causes by 14% and decrease risk of hospitalization related to cardiovascular issues by 23%.

The trial contains some limitations, such as lower-than-expected cardiovascular events. Adverse events associated with treatment included ketoacidosis, lower limb amputation, serious urinary tract infection, hyperkalemia, acute kidney injury, serious dehydration, and liver injury, but these are no worse in the placebo arm.

“Treatment with empagliflozin was effective…with respect to the primary outcome [and] was generally consistent across prespecified key subgroups and other prespecified subgroups,” the study authors wrote.

Reference

The EMPA-KIDNEY Collaborative Group*. Empagliflozin in Patients with Chronic Kidney Disease. Accessed January 17, 2023. N Engl J Med 2023;388:117-27. DOI: 10.1056/NEJMoa2204233