Empagliflozin Cuts Risk of Cardiovascular Death, More Severe CKD by 28%, Study Finds


Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduced the risk of death or worsening progression of chronic kidney disease (CKD) by 28%, according to results published Friday at Kidney Week 2022.

Patients with chronic kidney disease (CKD) at risk for progressing to worse disease or dying from cardiovascular issues had a 28% reduced risk of these outcomes when treated with empagliflozin, according to trial results released early Friday at Kidney Week 2022.

The randomized, double-blind, placebo-controlled trial, EMPA-KIDNEY, formally called the Study of Heart and Kidney Protection With Empagliflozin, was stopped early in March based on a recommendation from the trial’s independent data monitoring committee after an interim assessment met prespecified criteria for positive efficacy.

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was first approved for patients with type 2 diabetes (T2D) in 2014; it is marketed as Jardiance by Eli Lilly and Boehringer Ingelheim.

The study, results of which were also published simultaneously in the New England Journal of Medicine,1 was designed to test empagliflozin across a wide variety of patients with CKD, including those with severely decreased kidney function (the G4 stage) and those with normal to mild or moderately increased albuminuria, or protein in the urine (the A1 or A2 stage).

The trial included 6609 individuals in 8 countries across 241 study sites. Of the group, 46% had diabetes and 27% had preexisting cardiovascular disease; 35% had stage G4 CKD and 48% were classified as having A1-A2 albuminuria. The underlying cause of CKD stemmed from a variety of reasons, including diabetic kidney disease, glomerular disease, hypertensive/renovascular disease, other, and unknown causes.

The patients included in EMPA-KIDNEY had not been included in other SGLT2 trials, said William G. Herrington, MD, a nephrologist and researcher at the University of Oxford.

Patients were required to be on a renin-angiotensin inhibitor if usage was indicated and tolerated. Those included in the trial had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 mL/min/1.73 m2 or who had an eGFR of at least 45 but less than 90 mL/min/1.73 m2 with a urinary albumin-to-creatinine ratio of at least 200.

Participants were randomly assigned 1:1 to receive empagliflozin (10 mg once daily) or matching placebo (3304 and 3305 patients, respectively).

The mean age at randomization was 63.8 years (13.9), 2192 (33%) were female and 3570 (54%) had no prior history of T2D.2

The primary composite outcome was death from cardiovascular disease or a worsening of CKD, defined as end-stage kidney disease (ESKD) leading to dialysis or kidney transplant, or death from kidney failure. CKD progression was measured by declines in kidney function, defined as a sustained decrease in eGFR to less than 10 mL/min/1.73 m2, which is a typical starting point for dialysis, or a sustained decrease in eGFR of at least 40%.

Secondary outcomes included the effect of empagliflozin on time to hospitalization for heart failure or cardiovascular death, hospitalizations from any cause, and time to death from any cause.

The results showed that over the median of 2 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 patients (13.1%) in the empagliflozin group and in 558 patients (16.9%) in the placebo group (HR, 0.72; 95% CI, 0.64-0.82; P <.001).

Results were consistent among patients with or without diabetes and across subgroups, said Herrington.

The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (HR, 0.86; 95% CI, 0.78-0.95; P = .003).

However, there were no significant between-group differences with respect to the composite of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively.

In February, the FDA approved empagliflozin for a broader range of patients with heart failure, including those with preserved ejection fraction, or HFpEF—a condition with a poor prognosis and very limited treatment options. Empagliflozin has also been approved for HF with reduced ejection fraction, or HFrEF, regardless of T2D status, as of August 2021.

More details from the study will presented during the meeting Friday.


1. The EMPA-KIDNEY Collaboration Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med. Published online November 4, 2022. doi:10.1056/NEJMoa2204233

2. The EMPA-KIDNEY Collaborative Group. Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial. Nephrol Dial Transplant. 2022;37(7):1317-1329. doi:10.1093/ndt/gfac040

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