The prevention of disease progression and reducing cardiovascular risk are key treatment objectives for patients with CKD. Empagliflozin was originally developed to treat high blood sugar in people with diabetes but has recently been shown to have beneficial effects on both the heart and kidney. The EMPA-KIDNEY trial was set up to find out whether empagliflozin could benefit people who have kidney disease, whether they have diabetes or not.

The Challenge

CKD is present in about one-in-10 adults in the UK and it often leads to a gradual loss of kidney function over time. If you have CKD, you also have an increased risk of developing heart disease or having a stroke. Your condition may get worse, and you may need to have dialysis or a kidney transplant.

Previous clinical trials have demonstrated that drugs like empagliflozin, medicines called SGLT2 inhibitors used to lower blood glucose levels for adults with type 2 diabetes, helped reduce the risk of kidney disease becoming worse for diabetes patients. To understand whether this could provide benefits for CKD patients, there was a need to conduct a larger study including patients without diabetes and groups of patients who have been underrepresented in previous clinical trials of SGLT2 inhibitors.

The Solution

The EMPA-KIDNEY trial, led by the Medical Research Council Population Health Research Unit at the University of Oxford, part of Oxford Population Health, evaluated the efficacy and safety of empagliflozin in people with CKD at risk of kidney disease progression.

The study, part-funded by HDR UK, took place between 2019 and 2021 and included 6609 people with CKD from eight countries in Europe, North America and East Asia. It included people with and without diabetes. Half of the participants were randomly assigned a 10mg daily dose of empagliflozin and half were assigned a placebo, to ensure results are reliable and trustworthy.

The Impact

Since the Impact Committee selection of this paper, the team has released study results that demonstrate that empagliflozin reduces the risk of kidney disease progression or death from cardiovascular disease by 28% in people with CKD with similar benefits for participants with and without diabetes. The trial results are also part of a pool of 13 major trials that show empagliflozin and other SGLT2 inhibitors substantially reduce the risk of hospitalisation for heart failure and the risk of dying from cardiovascular disease in adults with CKD and other high risk conditions.

Will Herrington, lead author of the baseline paper in Nephrology Dialysis Transplantation and the main trial results in The New England Journal of Medicine said:

Thanks to the commitment of the trial participants and our collaborators around the world, we now know that empagliflozin reduces the risk of kidney disease progression or death from cardiovascular disease significantly in patients with, and without, diabetes.

“Slowing chronic kidney disease progression and avoiding the need for dialysis or a kidney transplant is highly desirable due to the adverse effects on quality of life, and the increased risk of cardiovascular disease.”

The results suggest that SGLT-2 inhibitors, such as empagliflozin, should be offered to all adults who may benefit from the treatment, to reduce the risk of kidney disease progression and cardiovascular complications in people with CKD.

What the Impact Committee said:

The Committee selected this research as it was designed to definitively answer a key clinical question, recruited a diverse and large population of people, and has produced results which represent a major advance in the treatment of patients with CKD, a condition where there are only a small number of proven therapies.