A landmark clinical trial has provided “renewed optimism” for patients with type 2 diabetes and kidney disease, after researchers found a drug reduced the risk of renal failure by almost a third.
In the study, researchers found that the drug canagliflozin minimised the risk of end-stage kidney disease in people with type 2 diabetes by 30%.
“We have a therapy for patients with type 2 diabetes and chronic kidney disease that decreases kidney failure”
The results have been described as the “first significant progress” in the treatment of chronic kidney disease for people with type 2 diabetes for nearly 20 years.
Findings from the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study were published this week in the New England Journal of Medicine and also presented at the World Congress of Nephrology in Melbourne.
The trial, which was stopped early in July 2018 due to conclusive results, was conducted in more than 4,400 adults living with type 2 diabetes worldwide.
Primary results of the study found that participants who took canagliflozin were 30% less likely than the placebo group to develop kidney failure or die from either renal failure or cardiovascular disease.
In addition, the risk of kidney failure or death from kidney failure was reduced by 34%, and the risk of hospitalisation for heart failure or death due to cardiac causes, decreased by 31%.
“The exciting results from the CREDENCE study provide renewed optimism for these patients”
Rates of adverse events and serious adverse events were similar overall in the canagliflozin group and the placebo group. For example, the study authors highlighted that there were no observed differences in the incidence of lower limb amputations or adjudicated fractures.
In the UK, canagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise. The initiation dose is 100mg once daily in adults with and can be increased to 300mg once daily if tighter glycaemic control is needed.
Professor Kenneth Mahaffey, from the Stanford University school of medicine in the US and co-principal investigator of the trial, said: “For the first time in 18 years, we have a therapy for patients with type 2 diabetes and chronic kidney disease that decreases kidney failure.
“Now, patients with diabetes have a promising option to guard against one of the most severe risks of their condition,” he added.
Lead study author Vlado Perkovic, executive director of the George Institute for Global Health Australia and a professor of medicine at the University of New South Wales in Sydney, said: “People with diabetes and kidney disease are at extremely high risk of kidney failure, heart attack, stroke and death.
“With this definitive trial result, we now have a very effective way to reduce this risk using a once-daily pill,” he added.
“The important question around fractures and amputations has been well addressed”
Around 40% of the people living with type 2 diabetes may go on to develop irreversible diabetic kidney disease – at an annual cost to the NHS between £532-927m.
People with diabetes can develop kidney disease because prolonged high blood sugar harms blood vessels in the kidney.
According to Stanford Medicine which supported the research, for the past two decades, physicians have largely relied on RAAS blockade to prevent the deterioration of kidney function in diabetic patients.
Although RAAS blockade lowers blood pressure and delays progression of kidney disease, patients undergoing the treatment remain at a high risk for renal failure and cardiovascular disease, as well as death from these conditions.
Commenting on the study, David Wheeler, professor of kidney medicine at University College London and honorary consultant nephrologist at the Royal Free NHS Foundation Trust, said: “We have been waiting for new drugs to help us manage these patients for almost 20 years.
“The exciting results from the CREDENCE study provide renewed optimism for these patients,” he added.
Source: Stanford Medicine News Center
Andrea Brown, from the National Kidney Federation, also said: “Effectively managing chronic kidney disease is a rapidly growing challenge for the NHS and we welcome any research that helps improve the management of this debilitating complication of type 2 diabetes.
“The exciting research from CREDENCE is the first positive dedicated trial of an antidiabetic agent in this area, showing how under-recognised the irreversible impact of chronic kidney disease and type 2 diabetes has been up until now,” she said.
Julie Brake, diabetes specialist nurse in Liverpool, said: “The study population in CREDENCE closely matched the characteristics of people we regularly see in practice which gives real value to the results.
“The important question around fractures and amputations has been well addressed with the comprehensive data from the study results,” she added.
The work was funded by pharmaceutical company Janssen, which manufactures canagliflozin.
In the UK, canagliflozin is sold by Napp Pharmaceuticals Ltd.