FDA Approves Empagliflozin for Adults With Chronic Kidney Disease at Risk of Progression

The FDA has approved empagliflozin (Jardiance; Boehringer Ingelheim, Eli Lilly and Company) 10 mg tablets to reduce the risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, cardiovascular death, and hospitalization for adults with chronic kidney disease (CKD) at risk of progression.

"This approval provides health care professionals in the [United States] with another treatment option for adults with CKD that can reduce the risk of kidney function decline, kidney failure, cardiovascular death, and hospitalizations," Katherine Tuttle, MD, executive director for research of Providence Inland Northwest Health, said in a statement. "The meaningful benefits that empagliflozin demonstrated in the EMPA-KIDNEY phase 3 trial [(NCT03594110)] are welcome news for adults living with CKD in this country."

The approval was based on data from the EMPA-KIDNEY trial, which investigated empagliflozin in adults with CKD, with or without type 2 diabetes (T2D), and included more than 6600 patients. The patients were included if they had an eGFR of 20 or greater to less than 45 mL/min/1.73 m2 or an eGFR of 45 or greater to less than 90 mL/min/1.73 m2 and had a urine albumin to creatinine ratio of 200 mg/g or greater.

Further, patients were excluded if they had T2D and prior atherosclerotic cardiovascular disease with eGFR below 60 mL/min/1.73 m2, type 1 diabetes (T1D), a functioning or scheduled kidney transplant, dialysis, polycystic kidney disease, a recent history of intravenous immunosuppressive therapy, or greater than 45 mg of prednisone or equivalent as treatment for kidney disease.

The results of the study showed that empagliflozin demonstrated a 28% relative risk reduction, with an absolute risk reduction of 3.6% per patient-year at risk, compared to placebo when used with the standard of care, for the composite primary endpoint of kidney disease progression or cardiovascular death. Investigators defined kidney disease progression as end-stage kidney disease, a sustained decline in eGFR to below 10 mL/min/1.73 m2, kidney death, or sustained decline of at least 40% in eGFR from randomization. Furthermore, the event rate for empagliflozin was 13.1% compared to the placebo at 16.9%.

According to the investigators, this was the first trial of an SGLT2 inhibitor for CKD that demonstrated a significant reduction in the risk of first and recurrent hospitalizations, showing a 14% relative risk reduction compared to the placebo. They reported that there were 1611 hospitalizations among 960 patients with empagliflozin and 1895 hospitalizations among 1035 patients with the placebo.

"Following previous indications for [empagliflozin] in heart failure and [T2D], this FDA approval now provides physicians, including nephrologists, with an important treatment option for adults living with CKD at risk for progression," Leonard Glass, MD, FACE, senior vice president of Diabetes Global Medical Affairs at Eli Lilly, said in a statement. "Alongside the recent CKD approval for [empagliflozin] in the [European Union], this decision further bolsters our efforts to support this community globally."

This is the fourth FDA approval for empagliflozin based on data from the EMPOWER program.

Empagliflozin is not recommended for the improvement of glycemic control for those with T1D as it may increase the risk of diabetic ketoacidosis. Further, it is not recommended for use to improve glycemic control for those with T2D who have an eGFR less than 30 mL/min/1.73 m2 as it would likely be ineffective. Lastly, it is not recommended for those with CKD with polycystic kidney disease, those who require or have a history of intravenous immunosuppressive therapy, or greater than 45 mg of prednisone or equivalent for kidney disease as it is not expected to be effective.

Reference

US FDA approves Jardiance for the treatment of adults with chronic kidney disease. News release. September 22, 2023. Accessed September 22, 2023. https://investor.lilly.com/news-releases/news-release-details/us-fda-approves-jardiancer-treatment-adults-chronic-kidney