FDA OKs Canagliflozin to Curtail Diabetic Kidney Disease

Megan Brooks

September 30, 2019

The US Food and Drug Administration (FDA) has approved canagliflozin (Invokana, Janssen) to reduce the risk of end-stage kidney disease, worsening of kidney function, cardiovascular death, and heart failure hospitalization, in adults with type 2 diabetes and diabetic kidney disease.

The new indication for the sodium-glucose cotransporter-2 (SGLT2) inhibitor follows results of the landmark CREDENCE trial, says Janssen.

"CREDENCE was a really ambitious trial because it specifically targeted individuals with significant chronic kidney disease — a group typically excluded from clinical trials," commented Medscape Medical News contributor and nephrologist F. Perry Wilson, MD, MSCE, Yale School of Medicine, New Haven, Connecticut.

"That ambition seems to have paid off with this new FDA indication. Of course, docs often prescribe meds 'off-label' — and many of us nephrologists have been prescribing SGLT2 inhibitors in this patient population already, but the approval from the FDA is a welcome show of support," said Wilson.

"Clearly, there is a new weapon in our diabetic kidney disease armamentarium," he added.

A Game-Changer

Canagliflozin was first approved for the treatment of type 2 diabetes by the FDA and the European Medicines Agency in 2013.

That indication was expanded in 2018 to include reduction in the risk of major adverse cardiovascular events in adults with type 2 diabetes who have established cardiovascular disease.

In the CREDENCE trial of patients with type 2 diabetes and chronic kidney disease, canagliflozin was associated with a 30% reduction in the risk of the primary composite endpoint, comprising end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death, as reported by Medscape Medical News.

The results also showed canagliflozin reduced the risk of secondary cardiovascular endpoints, including a 39% reduction in the risk of hospitalization for heart failure.

The CREDENCE results were presented during a late-breaking clinical trials session in April at the International Society of Nephrology (ISN): 2019 World Congress and simultaneously published in the New England Journal of Medicine.

"This is a game-changer, a whole new strategy we can use," study coauthor Meg Jardine, MBBS, PhD, from The George Institute for Global Health, Sydney, Australia, told Medscape Medical News at the time.

"Patients in the CREDENCE trial got the standard of care and investigators were encouraged to optimize their blood sugar and blood pressure control, but even beyond that we saw these powerful effects," Jardine said.

In the United States, one in three people with type 2 diabetes has diabetic nephropathy, which multiplies the risk of cardiovascular complications and puts patients on a trajectory to dialysis and kidney transplant.

"Millions of type 2 diabetes patients around the world have diabetic kidney disease and almost half of them aren't even aware of it. By the time they are referred to a nephrologist, it is often too late because their disease has progressed to the point where dialysis is inevitable," CREDENCE study investigator George Bakris, MD, University of Chicago, Illinois, said in the Janssen release.

"For nearly two decades, we've been searching for a treatment that can help us intervene earlier to slow kidney disease progression," he said.

"With the approval for this new indication for Invokana, physicians will not only be able to help reduce the risks associated with diabetic kidney disease but also reduce the risk of hospitalization for heart failure in [these] patients," said Bakris.

In June, the American Diabetes Association (ADA) updated its Standards of Medical Care in Diabetes to incorporate the findings from CREDENCE.

Renal outcomes trials with other SGLT2 inhibitors, including Dapa-CKD with dapagliflozin (Forxiga/Farxiga, AstraZeneca), in 4000 patients, and EMPA-KIDNEY with empagliflozin (Jardiance, Boehringer Ingelheim/Lilly), in around 5000 patients, are ongoing.

Wilson has reported no relevant financial relationships.

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