A recent trial of empagliflozin expanded the understanding of how the drug can slow chronic kidney disease in a wide range of patients, lowering the risk of disease progression and death from cardiovascular causes in patients with and without diabetes compared with a placebo.
The EMPA-KIDNEY trial, halted early for efficacy, recently had its results published in the New England Journal of Medicine. University of Oxford CTSU served as the global coordinator for the randomized, double-blind, controlled trial, while the Duke Clinical Research Institute served as the United States coordinating center.
The trial is the largest of the three large outcomes trials conducted in people with chronic kidney disease (CKD) that assessed the effects of SGLT2 inhibitors — drugs that were originally approved to lower blood sugar levels in type 2 diabetes by reducing reabsorption of glucose in the kidney.
Chronic kidney disease is common — estimated to affect 1 in 7 adults in the United States— and is a leading cause of death worldwide.
“In the previous outcomes trials, what we learned, largely in people with type 2 diabetes and chronic kidney disease and a lot of albumin in their urine, is that SGLT2 inhibitors delay the progression of kidney disease,” said Jennifer Green, MD, a member of the DCRI, principal investigator of the trial U.S. coordinating center and member of the trial executive committee. “They help to slow the worsening of kidney damage and kidney function over time. They also reduce the risk of cardiovascular events at the same time.”
To understand how empagliflozin works in a broader range of the CKD population, researchers enrolled a diverse set of patients with more varying manifestations of kidney disease than had previously been studied. EMPA-KIDNEY included 6,609 patients with or without diabetes, including individuals with an estimated glomerular filtration rate (eGFR) as low as 20 (indicating very impaired kidney function) who were not required to have large amounts of albumin in their urine. These patients with CKD had not been included in the prior studies.
“In EMPA-KIDNEY, we saw that the kidney and cardiovascular outcome benefits extended to people with very low eGFRs, who had been excluded from previous trials, and that empagliflozin slowed kidney disease progression across the spectrum of eGFR categories. Even in patients with very advanced kidney disease (with a very low eGFR value), empagliflozin still helped to arrest the worsening over time that we otherwise expect to see.”
Although researchers found empagliflozin to be beneficial across the entire patient population, it was particularly beneficial in individuals with a significant degree of albuminuria.
“The people with less albumin, interestingly, did not have a lot of the kidney and cardiovascular events that were included in the primary endpoint — their kidney disease did not progress as quickly and they did not have as many cardiovascular events as participants with higher levels of albuminuria,” Green said. “We didn’t detect a significant reduction in the risk of the primary outcome in people with normal levels of albuminuria. But, when we looked at other outcomes in the albuminuria groups it was clear that empagliflozin slowed the rate of decline in eGFR across all albuminuria categories.”
WHAT’S PREVENTING WIDER ADOPTION OF EMPAGLIFLOZIN FOR PEOPLE WITH CKD?
While chronic kidney disease affects an estimated 15 percent of Americans, 40 percent of individuals with severely reduced kidney function do not know they have CKD.
The first step to wider adoption of helpful therapies is to screen and identify people with chronic kidney disease, Green said, and then to make the diagnosis clearly recognizable in those patients’ medical records so that the effective therapy can be implemented.
Screening for kidney disease should happen as soon as a person is diagnosed with Type 2 diabetes, and it should include both measurement of the patient’s eGFR and an assessment of their albumin-to-creatinine ratio.
But it doesn’t always happen that way.
“In the United States, we’re OK at checking the eGFR once a year in people with type 2 diabetes, but we do very poorly in screening people for albuminuria, despite the fact that these recommendations have been in place for decades,” Green said. “The other thing that happens in the United States, is that even when people have abnormal labs, they’re not always identified in the medical record as having chronic kidney disease.”
FOLLOW-UP STUDY IN PROGRESS
The EMPA-KIDNEY research team is now conducting a long-term follow-up study involving many of the patients from the EMPA-KIDNEY trial, observing how the participants will do over longer periods of time. It will also be important to understand how many take open-label SGLT2 inhibitors following the completion of the initial study.