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11-04-2022 | Empagliflozin | News | Article

EMPA-KIDNEY supports SGLT2 inhibition for chronic kidney disease

Author: Eleanor McDermid

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medwireNews: Treating people with chronic kidney disease with the sodium-glucose cotransporter (SGLT)2 inhibitor empagliflozin significantly reduces their risk for renal disease progression or cardiovascular mortality, report the EMPA-KIDNEY investigators.

During a median 2.0 years of follow-up, 13.1% of 3304 study participants taking empagliflozin 10 mg/day had a primary outcome event (disease progression or cardiovascular mortality), compared with 16.9% of the 3305 participants given placebo, giving a significant 28% relative risk reduction in favor of empagliflozin treatment.

William Herrington (University of Oxford, UK) and co-researchers say this size of reduction is “quantitatively similar” to that reported for canagliflozin in CREDENCE, in which all participants had type 2 diabetes, and for dapagliflozin in DAPA-CKD, in which about two-thirds of the participants had the condition.

About 46% of the EMPA-KIDNEY participants had diabetes – primarily type 2 diabetes, although 2.2% had type 1 diabetes. Similar to both abovementioned trials, EMPA-KIDNEY was stopped early for “clear positive efficacy.”

Kidney disease progression was defined as end-stage kidney disease, a sustained reduction of estimated glomerular filtration rate (eGFR) to less than 10 mL/min per 1.73 m2, a sustained eGFR reduction of at least 40%, or death from renal causes. The trial recruited people with a baseline eGFR of at least 20 but less than 45 mL/min per 1.73 m2, or of 45 to less than 90 mL/min per 1.73 m2 but with an albumin-to-creatinine ration of at least 200. The average eGFR was 37 mL/min per 1.73 m2 and about a third of participants had an eGFR below 30 mL/min per 1.73 m2.

The participants were predominantly White (58%) or Asian (36%), were 64 years old on average, and about a quarter had a history of cardiovascular disease.

The reduced risk for the primary endpoint with empagliflozin versus placebo was driven by a 29% reduction in the risk for kidney disease progression. There was a nonsignificant 16% reduction in risk for heart failure hospitalization or cardiovascular death, but the researchers note that cardiovascular events occurred in only 4–5% of trial participants, which was a lower rate than expected and reduced the statistical power to detect differences in these endpoints.

“Nevertheless, the hazard ratios for the cardiovascular outcomes were consistent with the totality of the evidence to date,” they write in The New England Journal of Medicine.

In addition to having a reduced risk for the primary endpoint, people taking empagliflozin had a significant 14% reduction in the risk for hospitalization for any cause, at 24.8 versus 29.2 hospitalizations per 100 person–years.

Herrington and team say the trial “adds substantially to the existing evidence,” highlighting their finding of a consistent benefit of empagliflozin in people both with and without diabetes (significant hazard ratios of 0.64 and 0.82, respectively) and across the full range of included eGFRs (hazard ratios of 0.64–0.78).

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

N Engl J Med 2022; doi:10.1056/NEJMoa2204233


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