New Data Shows SGLT2 Inhibitors May Be Effective in Preventing Kidney Failure

New data presented at the American Society of Nephrology meeting in San Diego last November offers new hope to people with diabetes at risk of kidney disease and kidney failure. They suggest a new class of glucose-lowering agents, sodium glucose co-transporter type 2 (SGLT2) inhibitors, may be effective in preventing kidney failure.

This data has potential to be critically important. In 2010, there were approximately 2.5 million people globally with kidney failure receiving regular dialysis, or with a functioning kidney transplant. Those affected have a reduced life expectancy and quality of life. In addition, the costs of treatment are very large — in the United States, nearly 6 percent of the health budget is spent on providing dialysis to 0.2 percent of the population. These costs also lead to reduced access — recent estimates suggest that at least as many people die of kidney failure as start dialysis, due mostly to an inability to afford this expensive treatment. Furthermore, it is projected that the number of people receiving dialysis will double over the next 20 years. But despite that, the number of people dying of kidney failure due to lack of access to dialysis will continue to be similar to that seen today.

It is clear that preventing the development of kidney failure is the top priority in reducing the related burden of illness and cost. The leading cause of kidney failure around the world is type 2 diabetes, and the growing prevalence of diabetes suggests that prevention of diabetes-related kidney failure is key. Unfortunately, few proven treatments are currently available: angiotensin receptor blockers have been shown to prevent kidney failure in people with diabetes and kidney disease, and growing evidence suggests that intensive control of glucose levels may also be an important protective strategy. More treatments are urgently required.

So it is no wonder that the new data from the EMPA-REG outcomes trial, presented by Professor Christoph Wanner at the High Impact Clinical Trials session at the American Society of Nephrology meeting, was greeted by much excitement. This trial randomized over 7,000 people with diabetes and previous cardiovascular disease to the SGLT2 inhibitor Empagliflozin or to a matching placebo, and followed up for an average of approximately 3 years.

People who were randomized to Empagliflozin were previously reported to have a reduced rate of cardiovascular events and death. However, in a new analysis, it was also shown to have a 40 to 50 percent reduction in the likelihood of developing kidney failure, or having large reductions in kidney function.

These exciting results require confirmation: it was a post-hoc analysis and there was a relatively small number of events. But they do suggest that this is one of the most promising potential treatments currently available.

I have the privilege of leading the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) study Steering Committee. This trial is recruiting over 4,000 participants with diabetes and evidence of kidney disease, and randomizing them to the SGLT2 inhibitor Canagliflozin or to a matching placebo. It will formally assess the agent’s effects on the risk of kidney failure and cardiovascular death, and will reliably ascertain whether these exciting potential kidney protective effects are real.

If confirmed, these kidney benefits will transform the care of people with diabetes, and could dramatically reduce the number of people developing kidney failure as a result of diabetes around the world — preventing much individual suffering, premature death, and reducing health system costs around the world.

About the author:

Professor Vlado Perkovic MBBS, PhD, FRACP, FASN is Executive Director at The George Institute, parent organization of George Clinical. Perkovic, a nephrologist and internationally renowned researcher in kidney disease who heads the George Institute of Global Health Australia, conducts and leads international clinical trials and meta-analyses on kidney and cardiovascular disease, diabetes and blood pressure management. Perkovic led the development of George Clinical, the George Institute’s clinical trial arm, and has built strong relationships with international clinical trial groups, including in China and Asia. He is using these relationships to conduct key ‘public good’ trials.