Empagliflozin achieved a decrease in risk of kidney disease progression of 28% vs placebo in the most diverse population of patients in an SGLT-2 inhibitor trial.
Among a wide range of persons with chronic kidney disease (CKD) at high risk, the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin reduced the risk for disease progression or cardiovascular (CV) death by 28% vs placebo, according to findings from the landmark phase 3 EMPA-KIDNEY trial announced November 4th by scientific collaborators Boehringer Ingelheim and Eli Lilly.
The results were presented during the American Society of Nephrology (ASN)’s Kidney Week 2022 and published simultaneously online in the New England Journal of Medicine.
EMPA-KIDNEY also is the first such trial in which an agent in the class significantly reduced all-cause hospitalization (14%), a positive indicator for the health care system, study authors say, given the association of CKD with a 2-fold greater risk for hospitalization.
The US Food and Drug Administration in March 2020 granted empagliflozin fast track designation toward an approval for the drug's cardiorenal protective effects and EMPA-KIDNEY was stopped early in March 2022 by an independent monitoring board based on the significantly positive results-to-date.
EMPA-KIDNEY, according to a Lilly statement, is “the largest and broadest SGLT-2 inhibitor trial in CKD." Participants in the study had a wide range of comorobidities spanning CV, renal, and other metabolic conditions and CKD severity.
"The design of the EMPA-KIDNEY trial included a wider range of patients than ever before," said Professor Richard Haynes, co-principal investigator, in the statement. "Previous SGLT2 inhibitor trials focused on certain groups of people living with CKD, such as those with diabetes or high levels of protein in their urine. Today's positive trial results across a broad CKD population reflect an opportunity to improve the treatment of this disease and prevent people from needing dialysis."
Haynes and colleagues from the EMPA-KIDNEY Collaborative Group designed the multinational, randomized, placebo-controlled trial to assess the effect of empagliflozin on the primary outcome they defined as time to a first event – either a composite of progression of kidney disease (end-stage kidney disease, sustained decrease in eGFR to <10 ml/min/1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from CV causes.
The final cohort numbered 6609 patients both with and without diabetes and with and without albuminuria who were randomized to empagliflozin 10 mg/day or matching placebo. Median follow up was 2 years, during which Haynes and team observed progression of kidney disease or death from CV causes in 13.1% (432 of 3304) of patients in the empagliflozin group and in 16.9% (558 of 3305) of patients receiving placebo (hazard ratio [HR], 0.72; 95% CI, 0.64 to 0.82; P<.01).
Importantly the authors report that these results were consistent whether patients had T2D or not. In analysis across subgroups defined according to eGFR ranges, they write, the results remained consistent as well.
The investigators also report that the rate of hospitalization for any cause was lower in the empagliflozin group than in the placebo group (HR, 0.86; 95% CI, 0.78 to 0.95; P=.003).
However, when they evaluated reductions in key secondary endpoints of hospitalization for heart failure (HF) or CV death (empagliflozin 4.0%, placebo 4.6%) or death from any cause (4.5% and 5.1%, respectively) researchers found no significant differences.
Hayes and colleagues suggest that the power to detect statistically significant differences in the key secondary outcome events was limited by the small number of events themselves but note that the risk reduction seen in this study is consistent with the totality of evidence from other trials.
The overall safety data were generally consistent with previous findings, confirming the well-established safety profile of empagliflozin, Lilly says.
"We know that there is an urgent need for new therapies proven to delay CKD progression which can lead to the need for dialysis or transplantation. Today's results demonstrate that Jardiance may benefit adults at risk of progression, including those with or without diabetes, and across a wide range of kidney function," said William Herrington, associate professor at the Medical Research Council Population Health Research Unit at the University of Oxford, honorary consultant nephrologist, and EMPA-KIDNEY co-principal investigator.
"By reducing the risk of kidney disease progression or cardiovascular death, Jardiance has the potential to positively impact healthcare systems worldwide."
Empagliflozin has been approved to reduce the risk of CV death in adults with T2D and established CVD, and the risk of CV death in patients with HF.
In February 2022, the FDA approved empagliflozin for patients with HF, regardless of ejection fraction, to reduce the risk of CV death and hospitalization for HF.
Reference: Herrington WG, Staplin N, Wanner C, et al for the EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. New Engl J Med. Published online November 4, 2022. doi:10.1056/NEJMoa2204233