Canagliflozin reduces the risk of End-Stage Kidney Disease in T2DM patients:Results from the landmark trial(CREDENCE)

M3 India Newsdesk Apr 17, 2019

Summary

Results from the CREDENCE trial discussed at the 2019 World Congress of Nephrology prove the efficacy of the drug canagliflozin, initially developed to lower blood glucose, also reduces the risk of kidney failure in patients with diabetes and renal disease.


Researchers presented the results of three internationally relevant clinical trials which may change the way kidney disease is treated globally, at the World Congress of Nephrology (April 12 - 15, 2019) at Melbourne, Australia. The International Society of Nephrology live-streamed the sessions worldwide on April 15 from 8:30 AM to 10:30 AM AEST.

The first of these trials is a new treatment for kidney disease. It offers hope for hundreds of millions of patients with diabetes worldwide. Professor Vlado Perkovic and Associate Professor Meg Jardine from The George Institute for Global Health, and Professor Ken Mahaffey from Stanford University in the United States, presented at the meeting the results of the study known as the CREDENCE (Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation) trial.

The study revealed that in patients with diabetes and kidney disease, the use of the drug has reduced heart failure by over 30% and major cardiovascular events by about 20%. The New England Journal of Medicine published it today (April 15, 2019).

“Overall, the importance of CREDENCE, a well done and large clinical trial, cannot be overstated” the journal said in an accompanying editorial.


CREDENCE

The CREDENCE trial recruited 4,401 patients with diabetes and kidney disease from 34 countries. Half of the patients received canagliflozin on top of the best available care for kidney disease as per current guidelines- using either angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). The control group received the best available care, and a placebo.

The researchers stopped the trial in July 2018 as the treatment has already shown its efficacy. They consider that the study offers the first new therapy in more than 15 years for slowing the progression of chronic kidney disease in patients with type 2 diabetes. They suggested that as the drug is readily available, physicians can start treatment immediately. Canagliflozin is a drug presently used to treat Type 2 diabetes

The study shows that the drug canagliflozin which researchers developed to lower glucose levels for people with diabetes protects against kidney failure besides significantly reducing the risk of cardiovascular complications including heart failure, which are common among people with kidney disease.

Professor Vlado Perkovic, the lead author pleaded that there was an urgent need for this new treatment given the surging rates of diabetes.

"Diabetes is the leading cause of kidney failure worldwide but for almost two decades there have been no new treatments to protect kidney function. This definitive trial result is a major medical breakthrough as people with diabetes and kidney disease are at extremely high risk of kidney failure, heart attack, stroke and death. We now have a very effective way to reduce this risk using a once daily pill.” a press release quoted him

"With five million people worldwide predicted to have kidney failure by 2035 this is a major breakthrough." Associate Professor Meg Jardine from The George Institute for Global Health added


Key findings listed by a press release

  1. The number of people developing kidney failure or dying from either kidney failure or cardiovascular disease was reduced by 30%.
  2. Incidents of hospitalisation for heart failure were reduced by 39%.
  3. The risk of major cardiovascular outcomes - heart attack, stroke and cardiovascular death - was reduced by 20%.
  4. There was no increased risk of major side effects.

The researchers found canagliflozin, less effective at lowering blood sugar in people with reduced kidney function but still led to less kidney failure, heart failure and cardiovascular events such as heart attacks, strokes and death from cardiovascular disease.

Janssen, which manufactures canagliflozin, funded the randomized study and an independent, academic- led Steering Committee led the study


Relevance to India

The present study is very relevant to India, when we consider some of the scary details of the disease. Writing in The Hindustan Times (March 14, 2019), Dr V Mohan, a leading diabetologist stated thus: there are 72 million people with diabetes in India; they may increase to 134 million in the next 10-15 years; after 15 to 20 years of having diabetes, nearly a third of people with the condition develop kidney complications. Obviously, managing them is a daunting task. The new treatment may turn out to be very beneficial to India


A Clinical Trial of IntensiVE (ACTIVE) Dialysis Study

Dr Brendan Smyth, of The George Institute for Global Health presented the second study A Clinical Trial of IntensiVE (ACTIVE) Dialysis Study which reports on the long-term outcomes of a study to see whether intensive dialysis of 24 hours per week or more would improve the health and quality of life for people with end stage kidney disease.

The ACTIVE Dialysis Study involved 200 randomised participants from China, Australia, New Zealand and Canada. They received either 24 hours or 12 hours of dialysis per week for 12 months. At the end of that period there was no difference in overall quality of life although there were small but potentially important improvements in some quality of life domains.


The Study of Diabetic Nephropathy with Atrasentan (SONAR) trial

Professor Dick de Zeeuw, from the University of Groningen in The Netherlands and colleagues presented the third trial -The Study of Diabetic Nephropathy with Atrasentan (SONAR)

Researchers designed SONAR trial to determine if treatment with the investigational medicine atrasentan, when added to standard-of-care therapies, was safe and could improve prognosis by delaying the onset of progression or end stage renal disease in type 2 diabetic patients at high risk for losing kidney function.

Researchers initially screened over 11,000 patients with stage 2-4 chronic kidney disease for the trial, more than 4,700 patients among them completed a six-week "enrichment period" to gauge their response to a daily dose of atrasentan. Following the enrichment period, 2,648 patients responded to treatment and met the pre-defined criteria to continue on to randomization to treatment with atrasentan added to the standard-of-care or placebo added to the standard-of-care.

The researchers randomised an additional 1,020 patients who did not respond initially to treatment during the enrichment period and offered them treatment with atrasentan or placebo plus the standard-of-care. A median follow-up of 2.2 years among the patients who responded to atrasentan during the enrichment period demonstrated that treatment with atrasentan plus the standard-of-care reduced the rate of the primary renal endpoint by 35 percent, compared to placebo.

The International Society of Nephrology (ISN) is “a philanthropic organization dedicated to advancing worldwide kidney health” .The Indian Society of Nephrology collaborates closely with ISN.

 

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The writer, Dr. K S Parthasarathy is a freelance science journalist and a former Secretary of the Atomic Energy Regulatory Board

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