Positive results were announced from a phase 3 trial evaluating the effect of empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, on kidney disease progression or cardiovascular (CV) death in patients with pre-existing chronic kidney disease (CKD).

The multicenter, randomized, parallel-group, double-blind, placebo-controlled EMPA-KIDNEY trial (ClinicalTrials.gov Identifier: NCT03594110) enrolled more than 6600 patients 18 years of age and older with CKD at risk of kidney disease progression. The study population included patients with or without diabetes, with mildly to severely reduced eGFR, and with normal and increased levels of albumin.

Patients were randomly assigned to receive empagliflozin 10mg or placebo once daily. The primary composite endpoint was the time to first occurrence of kidney disease progression (defined as end stage kidney disease with a sustained decline in eGFR <10mL/min/1.73m2, renal death, or a sustained decline of ≥40% in eGFR) or CV death.

Results showed that treatment with empagliflozin reduced the risk of kidney disease progression or CV death by 28% compared with placebo (hazard ratio [HR], 0.72; 95% CI, 0.64-0.82; P <.000001). Additionally, a 14% reduction in all-cause hospitalization (secondary endpoint) was observed with empagliflozin when compared with placebo (HR, 0.86; 95% CI, 0.78-0.95; P =.0025). Differences in other key secondary endpoints including hospitalization for heart failure or CV death or all-cause death were found not to be statistically significant. The overall safety profile of empagliflozin was generally consistent with its established profile.

Commenting on the findings, Professor Richard Haynes, co-principal investigator, said: “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.”

Empagliflozin is marketed under the brand name Jardiance® and is currently indicated to improve glycemic control as an adjunct to diet and exercise in adults with type 2 diabetes mellitus (T2DM); to reduce the risk of CV death in adults with T2DM and established CV disease; and to reduce the risk of CV death and hospitalization for heart failure in adults with heart failure independent of left ventricular ejection fraction.

References

  1. Landmark EMPA-KIDNEY trial showed significant benefit of Jardiance® in reducing kidney disease progression or cardiovascular death by 28% vs. placebo in people with chronic kidney disease. News release. Boehringer Ingelheim and Eli Lilly and Company. Accessed November 4, 2022. https://www.businesswire.com/news/home/20221104005412/en/Landmark-EMPA-KIDNEY-trial-showed-significant-benefit-of-Jardiance%C2%AE-in-reducing-kidney-disease-progression-or-cardiovascular-death-by-28-vs.-placebo-in-people-with-chronic-kidney-disease
  2. The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. Published online November 4, 2022. NEJM. doi: 10.1056/NEJMoa2204233.