EMPA-KIDNEY Trial Shows Jardiance Reduces Chronic Kidney Disease Progression, Cardiovascular Death Risk, with Benefits Lasting Up to One Year Post-Treatment
EMPA-KIDNEY trial shows that two years of treatment with Jardiance (empagliflozin) significantly lowered the risk of chronic kidney disease progression and cardiovascular death, with lasting cardiorenal benefits up to one year after treatment ended.
Credit: mi_viri | stock.adobe.com
Long-term results of the Phase III EMPA-KIDNEY trial (NCT03594110) demonstrate that two years of treatment with Jardiance (empagliflozin; Boehringer Ingelheim and Eli Lilly and Company) lowered the risk of chronic kidney disease (CKD) progression and cardiovascular death, with cardiorenal benefits observed for up to one year after the Jardiance regimen was discontinued.1,2 The data, published by The New England Journal of Medicine, were consistent over a two-year period across a population of patients with a wide range of CKD causes and levels of kidney function and albuminuria. The study authors noted that their findings highlight the potential need for long-term therapy with sodium glucose cotransporter-2 (SGLT2) inhibitors to maximize cardiorenal benefits in this patient population.
“In our current report on the results of a 2-year post-trial observation period in which the original group-assignment blinding was maintained, we found that similar percentages of patients in the two groups received open-label SGLT2 inhibitors and that there were important residual cardiorenal benefits from assignment to the empagliflozin group after the trial drug was discontinued,” the study authors wrote. “If there had been no off-treatment effect of empagliflozin post-trial (i.e., if the hazard ratio had been 1.0 after discontinuation of the trial drug), absolute benefits would be observed to diminish from the end of the active-trial period. Instead, we observed that absolute benefits both for a composite primary-outcome event and for death or end-stage kidney disease were initially maintained.”1
Jardiance has previously been approved to lower the risk of cardiovascular death (CVD) and hospitalization in adults with heart failure (HF); to lower the risk of further worsening of kidney disease, end-stage kidney disease, death from CVD, and hospitalization in adults with CKD; to lower the risk of CVD in adults with type 2 diabetes with known cardiovascular disease; and to reduce blood sugar in conjunction with diet and exercise in patients aged 10 years older with type 2 diabetes. Jardiance has previously been shown to reduce the risk of CVD or hospitalization for HF in patients with chronic HF with reduced left ventricular ejection fraction. Further, Jardiance has been found to reduce the risk of CVD or hospitalization for HF in patients with chronic HF with a preserved left ventricular ejection fraction.3
The authors of the current study sought to analyze the efficacy and safety of Jardiance in a broad range of patients with CKD at risk of progression. Results from the active portion of the EMPA-KIDNEY trial and other large trials show that SGLT2 inhibitors can substantially slow CKD progression and lower cardiovascular risk, in addition to reducing the risk of hospitalization for HF and acute kidney injury in patients with CKD and other high-risk conditions. Prior results from EMPA-KIDNEY show Jardiance met the trial’s primary endpoint, with CKD patients achieving a significant kidney and cardiovascular benefit. Patients administered the drug showed a reduced risk of kidney disease progression or cardiovascular death by 28% compared with placebo.4
The multinational, randomized, double-blind, placebo-controlled EMPA-KIDNEY trial analyzed the effect of Jardiance on kidney disease progression and cardiovascular mortality risk. The optional post-trial follow-up substudy was conducted at 185 of the 241 trial centers, with all surviving patients from the participating centers eligible for the follow-up.
Among 6609 patients randomly assigned during the active trial, 4891 were enrolled in the post-trial period, in which administration of open-label SGLT2 inhibitors was similar across the two cohorts, with 43% in the Jardiance cohort and 40% in the placebo cohort.
Across the combined active and post-trial periods, investigators observed a primary-outcome event in 26.2% of patients administered Jardiance compared with 30.3% in the placebo cohort (hazard ratio, 0.79; 95% confidence interval [CI], 0.72 to 0.87).
Results from the post-trial period show the hazard ratio for a primary-outcome event was 0.87 (95% CI, 0.76 to 0.99). Across the combined periods, the risk of kidney disease progression was 23.5% in the Jardiance cohort compared with 27.1% in the placebo cohort. The risk of the composite of death or end-stage kidney disease was 16.9% in the Jardiance cohort compared with 19.6% in the placebo cohort and the risk of cardiovascular death was 3.8% in the Jardiance cohort compared with 4.9% in the placebo cohort.
“Post-trial follow-up of our active-trial patients provided more complete quantification of the total effects of a short period of 2 years of empagliflozin treatment, including any carryover effect after stopping the trial drug,” the study authors concluded. “In a broad range of patients with chronic kidney disease, empagliflozin continued to have additional cardiorenal benefits for up to 12 months after it was discontinued.”1
References
1. EMPA-KIDNEY Collaborative Group. Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2024. Published October 25, 2024. DOI: 10.1056/NEJMoa2409183.
2. EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin). ClinicalTrials.gov. Updated October 18, 2024. Accessed October 30, 2024. https://clinicaltrials.gov/study/NCT03594110
3. Results announced from EMPACT-MI phase III trial investigating the effect of Jardiance® (empagliflozin) on risk of heart failure hospitalization and death in adults following a heart attack. Eli Lilly. News release. April 6, 2024. Accessed October 30, 2024. https://investor.lilly.com/news-releases/news-release-details/results-announced-empact-mi-phase-iii-trial-investigating-effect
4. 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. November 4, 2022. Accessed October 30, 2024. https://www.boehringer-ingelheim.com/us/human-health/chronic-kidney-disease/full-data-announced-phase-iii-empa-kidney-trial
Phase III MOVe-NOW Trial to Evaluate New Lagevrio Formulation Targeting High-Risk COVID-19 Patients
December 6th 2024Merck and Ridgeback Biotherapeutics have launched the Phase III MOVe-NOW trial to evaluate a new, streamlined formulation of Lagevrio (molnupiravir) for treating non-hospitalized COVID-19 patients at high risk of severe disease progression who are unable to use other antiviral therapies.
Phase II Piranga Trial Shows Promise of Xalnesiran Combination for Hepatitis B Treatment
December 5th 2024Phase II Piranga trial found that the combination of xalnesiran and an immunomodulator effectively reduced hepatitis B surface antigen (HBsAg) levels, but highlighted challenges in response durability and efficacy in patients with high HBsAg levels.
Zerlasiran Achieves Significant Sustained Reduction in Lipoprotein(a) Levels with Infrequent Dosing
November 20th 2024Zerlasiran, a novel siRNA therapy, demonstrated over 80% sustained reductions in lipoprotein(a) levels with infrequent dosing in the Phase II ALPACAR-360 trial, highlighting its potential as a safe and effective treatment for patients at high risk of cardiovascular disease.
