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Empagliflozin (Jardiance) reduced the risks of chronic kidney disease (CKD) progression and cardiovascular-related deaths in high-risk patients compared with placebo, the phase III EMPA-KIDNEY trial showed.

Over a median 2-year follow-up, CKD progression or cardiovascular-related death occurred in 13.1% of patients receiving empagliflozin 10 mg once daily compared with 16.9% of those receiving placebo (HR 0.72, 95% CI 0.64-0.82, P<0.001), meeting the trial's primary endpoint, reported William Herrington, MBBS, MD, of the University of Oxford in England, and colleagues.

The rate of hospitalization for any cause was also reduced with the SGLT2 inhibitor compared with placebo (24.8 vs 29.2 hospitalizations per 100 patient-years; HR 0.86, 95% CI 0.78-0.95, P=0.003), they noted.

These findings were presented at the American Society of Nephrology's Kidney Week and simultaneously published in the .

When looking at CKD progression alone -- defined as end-stage kidney disease, a sustained decrease in eGFR to less than 10 mL/min/1.73 m², a sustained decrease in eGFR of 40% or more, or death from renal causes -- this occurred in 11.6% of patients on empagliflozin versus 15.2% on placebo (HR 0.71, 95% CI 0.62-0.81).

Over the course of the trial, those on placebo also saw a steeper decline in eGFR, with a difference of 0.75 mL/min/1.73 m² (95% CI 0.54-0.96) between groups.

"The relative benefits were consistent in those with and without diabetes," said Herrington during a presentation of the findings, "and completely consistent across the full range of eGFR studied, down to at least 20 [mL/min/1.73 m²]."

However, when patients were broken down according to urinary albumin-to-creatinine ratio, the primary outcome only significantly favored empagliflozin in those with a baseline ratio above 300.

"But our chronic slope analyses suggest that empagliflozin slowed chronic decline irrespective of level of albuminuria," he noted.

Because of the trial's positive results, the Independent Data Monitoring Committee recommended the plug be pulled on the trial early, manufacturers jointly announced back in March.

"Worldwide 5 to 10 million people die each year from chronic kidney disease and many lives are severely disrupted by dialysis treatment," Herrington said in a statement. "We studied a wide range of patients with declining kidney function with the aim of delaying the need for dialysis and avoiding heart disease in as many of them as possible."

The authors noted that there wasn't a significant difference between the groups when it came to death from any cause (4.5% with empagliflozin vs 5.1% with placebo), or a composite outcome of hospitalization for heart failure or death from cardiovascular causes (4.0% vs 4.6%, respectively).

Active treatment was safe in this high-risk population, with a similar rate of serious adverse events occurring in both groups. Rates of ketoacidosis (0.2% vs <0.1%) and lower-limb amputations (0.8% vs 0.6%) were more common in the empagliflozin group.

The 241-center trial randomized 6,609 patients, all of whom had an eGFR of at least 20 but less than 45 mL/min/1.73 m² at baseline or an eGFR of 45 to <90 mL/min/1.73 m² but with a urinary albumin-to-creatinine ratio of at least 200.

Mean age was 63.8 years, 33.2% were women, and 54.0% were free of diabetes. At baseline, the mean eGFR was 37.3±14.5 mL/min/1.73 m², and 34.5% had an eGFR below 30. The median urinary albumin-to-creatinine ratio was 329, and 48.3% had a ratio of 300 or less.

Empagliflozin was first FDA approved in 2014 for type 2 diabetes. Since then, it's also picked up indications for risk reduction of cardiovascular death and hospitalization for heart failure regardless of ejection fraction.

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