The results were presented during the American Society of Nephrology (ASN) Kidney Week 2022 and published simultaneously online in the New England Journal of Medicine. EMPA-KIDNEY is also 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, the study authors say, given the association of CKD with a twofold higher risk of hospitalization. The US Food and Drug Administration in March 2020 granted empagliflozin designation to approve the cardiorenal protective effects of the drug, and EMPA-KIDNEY was stopped in early March 2022 by an independent monitoring board based on the significant positive results to date. EMPA-KIDNEY, according to a Lilly statement, is “the largest and most comprehensive trial of an SGLT-2 inhibitor in CKD.” “The design of the EMPA-KIDNEY trial included a wider range of patients than ever before,” Professor Richard Haynes, co-principal investigator, said 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 in a broad CKD population reflect an opportunity to improve the treatment of this disease and prevent people who they need 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 defined as time to a first event – either a composite of progression of renal disease (end-stage renal disease, sustained decline in eGFR to <10 ml/min/1.73 m2, sustained decline in eGFR ≥40% from baseline, or death from renal causes) or death from CV causes. The final cohort numbered 6609 patients 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 cardiovascular causes in 13.1% (432 of 3304) of patients in the empagliflozin group and in 16.9% ( 558 of 3305) of patients who received placebo (hazard ratio [HR]0.72; 95% Cl, 0.64 is 0.82; P < .01). Importantly, the authors report that these results were consistent whether patients had T2D or not. In the analysis between subgroups defined according to eGFR ranges, they write, the results also remained consistent. The researchers 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 assessed reductions in the key secondary endpoints of hospitalization for heart failure (HF) or cardiovascular death (empagliflozin 4.0%, placebo 4.6%) or death from any cause (4.5% and 5.1%, respectively), the researchers found no significant differences. Hayes and colleagues suggest that the power to detect statistically significant differences in key secondary outcome events was limited by the small number of events themselves, but note that the risk reduction observed in this study is consistent with the overall evidence from other tests. The overall safety data were generally consistent with previous findings, confirming empagliflozin’s well-documented safety profile, Lilly says. “We know there is an urgent need for new treatments proven to delay the progression of CKD that can lead to the need for dialysis or a transplant. Today’s results show that Jardiance may benefit adults who are at risk of progression, including those with or without diabetes , and across a wide range of kidney function,” said William Herrington, Associate Professor in 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 developing kidney disease or cardiovascular death, Jardiance has the potential to positively impact healthcare systems worldwide.” Empagliflozin is approved to reduce the risk of cardiovascular death in adults with T2D and established cardiovascular disease and the risk of cardiovascular death in patients with heart failure. In February 2022, the FDA approved empagliflozin for patients with heart failure, regardless of ejection fraction, to reduce the risk of cardiovascular death and hospitalization for heart failure. Citation: 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
