The landmark EMPA-KIDNEY trial showed that in patients with chronic kidney disease, empagliflozin significantly reduced the risk of renal disease progression or cardiovascular death by up to 28% compared with placebo

The EMPA-KIDNEY PHASE III clinical trial demonstrated significant renal and cardiovascular benefits in adult patients with chronic kidney disease (CKD), meeting its primary ^{endpoints [1],[2].}

The risk of renal disease progression or cardiovascular death was significantly reduced by 28% after taking empagliflozin compared with placebo (HR; 0.
72; 95% CI 0.
64 to 0.
82; P<0.
000001)^{[1], [2].}

The Population Health Research Unit (MRC PHRU) of the Medical Research Council of the University of Oxford presented its results during the American Society of Nephrology (ASN) Kidney Week 2022, which designed, conducted, and analyzed the EMPA-KIDNEY clinical trial with financial support
from Boehringer Ingelheim and Eli Lilly (NYSE:LLY).
The results were also published simultaneously in the New England Journal of Medicine ^[2].

The EMPA-KIDNEY study demonstrated for the first time that empagliflozin significantly reduced the risk of all-cause hospitalization (14%) in patients with CKD compared with placebo (HR; 0.
86; 95% CI 0.
78 to 0.
95; P = 0.
0025), which is a prespecified confirmatory endpoint [^1], ^[2].

CKD is the leading cause of death in patients worldwide and doubles the risk of hospitalization [^4],[5]
.
In the United States, hospitalization costs for patients with CKD account for 35 to 55 percent of total healthcare ^{costs [6].}

The overall safety data of this trial are generally consistent with previous studies and confirm the established safety profile
of empagliflozin.

"We urgently need new therapies
that have been proven to delay the progression of CKD to dialysis or transplantation.
The findings suggest that empagliflozin reduces the risk of disease progression in adult patients with or without diabetes, regardless of
renal function.
William Herrington, associate professor and associate professor at the Oxford Population Health Clinic, honorary consultant nephrologist and EMPA-KIDNEY co-principal investigator
.
By reducing the risk of renal disease progression or cardiovascular death, empagliflozin may have a positive impact
on the global healthcare system.
”

"The EMPA-KIDNEY trial is designed to include a broader patient base
than ever before.
" Co-principal investigator Professor Richard Haynes said
.
"Previous SGLT2 inhibitor trials have focused more on specific patients with CKD, such as those with comorbid diabetes or high levels of proteinuria
.
Today's positive trial results in patients with extensive CKD suggest that the drug has the potential to improve the outlook for more patients with CKD and avoid progression to dialysis
.
”

EMPA-KIDNEY is the largest and most extensive SGLT-2i trial to date focused on the CKD field ^[7].

The study included more than 6609 participants and covered a wide range of underlying causes, many of whom had comorbid cardiovascular, renal or metabolic disorders
.
This trial evaluated renal and cardiovascular outcomes in patients with varying severity of CKD ^[8].

"Boehringer Ingelheim and Eli Lilly's Diabetes Alliance are extremely proud that EMPA-KIDNEY has once again achieved this milestone for Otangjing," said
Carinne Brouillon, Head of Boehringer Ingelheim's Human Medicines business and a member of the Board of Directors.
"The data published by ASN provides a wealth of evidence for our clinical program, which includes more than 700,000 adults with
cardiovascular, renal and metabolic diseases.
EMPA-KIDNEY reinforces the important role
of empagliflozin in changing the way these interrelated diseases are managed.
”

There were no statistically significant reductions in other key secondary endpoints of hospitalisation for heart failure or cardiovascular death or all-cause death, but their testability was limited
by the number of events observed.
These reductions in the risk of events at these endpoints were consistent with
the corresponding results of other trials that were statistically significant.

"The EMPA-KIDNEY trial results will be welcomed
by CKD patients and the medical community.
We are also encouraged by the significant reduction in the risk of hospitalization observed after only two years of treatment, as this finding is consistent with the significant reduction in previous trials of empagliflozin cardiovascular outcomes," said
Jeff Emmick, MD, vice president of product development at Eli Lilly.
"The Alliance looks forward to discussing the marketing authorization program
for new indications for empagliflozin with regulators around the world in due course.
"

Professor Liu Zhihong, academician of the Chinese Academy of Engineering, director of the National Clinical Research Center for Kidney Diseases, and China's leading principal investigator, said, "The prevalence of CKD in adults over 18 years old in China is as high as 10.
8%, and the total number of patients is nearly 120 million [9].

CKD has become the 11th leading cause of death in China ^[10].

We are pleased that China has participated in the EMPA-KIDNEY large-scale clinical study, and a total of 986 Chinese CKD patients have been enrolled in 17 centers across the country, accounting for 15%
of the global enrollment.
It is expected that the empagliflozin CKD indication will be submitted to the market application in China as soon as possible, and the early approval will benefit the majority of CKD patients
in China as soon as possible.
”

Edit the comment

Renal disease progression: defined as end-stage renal disease (initiation of maintenance dialysis or renal transplantation), persistent decrease in glomerular filtration rate (eGFR) below 10 mL/min/1.
73 m2, renal death, or sustained reduction in eGFR of at least 40%
from randomization.

End-stage renal disease: including initiation of maintenance dialysis or receiving kidney transplantation

For more information about chronic kidney disease or metabolic conditions of the heart and kidneys, visit www.
boehringer-ingelheim.
com/chronic-kidney-disease

On EMPA-KIDNEY: a study of the protective effect of empagliflozin on the heart and ^{kidneys[1], [2], [8].}

EMPA-KIDNEY (NCT03594110) is a randomized, double-blind, placebo-controlled clinical trial conducted in multiple countries to evaluate the effect
of empagliflozin on renal disease progression and risk of cardiovascular mortality.
Primary outcomes were defined as cardiovascular death or first renal disease progression event, end-stage renal disease (requiring renal replacement therapy such as dialysis or kidney transplantation), persistent decline in eGFR to <10 mL/min/1.
73 ㎡, renal death, or a sustained decrease in eGFR since randomization ≥40%.

Key secondary endpoints included cardiovascular death or heart failure hospitalisation, all-cause hospitalization, and all-cause mortality
.
EMPA-KIDNEY included 6609 adult patients with CKD randomized from 8 countries, with or without diabetes, with or without proteinuria
.
Receive 10 mg of empagliflozin or placebo
on the basis of current standard therapy.

About the Population Health Research Group (PHRU) of the Medical Research Council (MRC) of the University of Oxford

The MRC PHRU at the University of Oxford is part of Oxford Population Health and aims to improve the treatment and prevention of chronic diseases, particularly cardiovascular and metabolic diseases such as diabetes and CKD
.
Together, these diseases constitute a large proportion of the global burden
of premature death and disability among adults.
MRC PHRU is led by Professor Colin Baigent, Co-Chair of the EMPA-KIDNEY Steering Committee
.
MRC PHRU coordinates innovative clinical trials and meta-analyses
that have significant health implications.
Other major studies include a groundbreaking randomised evaluation of the RECOVERY trial, co-chaired
by Professor Martin Landray, co-chair of the EMPA-REGINE Steering Committee.
MRC PHRU involves studies involving large populations worldwide, providing reliable information on the causes of disease and the effects of treatments, and has a significant impact
on global health.

About the EMPOWER project

The EMPOWER program, initiated by the Diabetes Alliance, aims to explore the effects of empagliflozin on major clinical cardiovascular and renal outcomes in a range of
cardiorenal metabolic diseases.
Cardiorenal metabolic diseases are the leading cause of death worldwide, causing up to 20 million deaths each year ^[11].

Through the EMPOWER project, Boehringer Ingelheim and Eli Lilly are working to increase understanding of these interrelated systems and develop treatments
that offer integrated, multi-organ benefits.
Comprised of nine clinical trials and two real-world evidence studies, EMPOWER aims to deepen the alliance's long-term commitment to improving outcomes for patients with cardiorenal metabolic diseases
.
With clinical studies enrolling more than 400,000 adult patients worldwide, EMPOWER is one of
the most extensive and comprehensive clinical programs for SGLT2 inhibitors to date.

About empagliflozin

Enpagliflozin (trade name Omotang Azine ^®) is an oral, once-daily, highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor and the first type 2 diabetes drug to include data on reducing the risk of cardiovascular death in many countries [^12],[13].

       References

       [1] [Insert EMPA-KIDNEY presentation at ASN]

       [2] [Insert EMPA-KIDNEY article published by NEJM]

[3] Iwagami M, Caplin B, Smeet L,et al.
Chronic kidney disease and cause-specific hospitalisation: a matched cohort study using primary and secondary care patient data.
British Journal of General Practice.
2018; 68(673): e512-e523.

       [4] USRDS.
2021 Annual Report.
[online] Last accessed: October 2022.

[5] Neuen BL, Chadban SJ, Demalo AR, et al.
Chronic kidney disease and the global NCDs agenda.
BMJ Glob Health.
2017; 2:e000380.

[6] Nichols GA, Ustyugova A, Déruaz-Luyet A, et al.
Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure .
JASN.
2020; 31 (7):1594-1601.

       [7] The EMPA-KIDNEY Collaborative Group.
[Published online ahead of print March 3, 2022].
Nephrol Dial Transplant.
2022.
DOI:10.
1093/ndt/gfac040.

       [8] Clinical Trials.
EMPA-KIDNEY (The Study of Heart and Kidney Protection With Empagliflozin).
Available at: https://clinicaltrials.
gov/ct2/show/NCT03594110 Last accessed: October 2022.

       [9] Zhang L, et al.
Prevalence of chronic kidney disease in China: a cross-sectional survey Lancet, 2012, 379(9818): 815-822.

       [10] GBD 2019[DB/OL]https://vizhub.
healthdata.
org/gbd-compare/#.

[11] GBD 2015 Mortality and Causes of Death Collaborators.
Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015.
Lancet.
2016; 388(10053):1459–544.

       [12] Jardiance? (empagliflozin) tablets.
European Product Information, approved April 2020.
Available at: Last accessed: October 2022.

       [13] Jardiance? (empagliflozin) tablets, U.
S.
Prescribing Information.
Available at: http://docs.
boehringer-ingelheim.
com/Prescribing%20Information/PIs/Jardiance/jardiance.
pdf.
Last accessed: October 2022.