Canagliflozin Improves Renal Outcomes for Diabetes Patients

George Bakris, MD

New data released about canagliflozin (Invokana) from the Canagliflozin Cardiovascular Assessment Study (CANVAS) show that the drug improved renal outcomes for patients with type 2 diabetes (T2D) who have or are at high risk for cardiovascular disease (CVD).

Canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reduced the urinary albumin to creatinine ratio (UACR), a key biomarker for chronic kidney disease, in people with both preserved and reduced kidney function, as measured by estimated glomerular filtration rate (eGFR) above or below 60 mL/min/1.73 m².

Over 30 million people in the US are living with diabetes, and about 25% of them are undiagnosed, according to the Centers for Disease Control and Prevention (CDC) estimates. Additionally, people with diabetes are twice as likely to have heart disease or a stroke as people without diabetes.

"Diabetic kidney disease remains the most common cause of end-stage renal disease worldwide, which underscores the need to further explore the potential renal protective effects of SGLT2 inhibitors," said George Bakris, MD, Professor of Medicine and Director, Comprehensive Hypertension Center, University of Chicago Medicine.

The drug resulted in a reduction in UACR in patients with preserved eGFR by 17% and reduced eGFR by 23%. Canaglifozin also resulted in a relative risk reduction of the composite endpoint (40% decline in eGFR, end-stage kidney disease, or renal death) by 47% in patients with preserved kidney function and 24% in patients with reduced kidney function.

Canagliflozin was first approved by the US Food and Drug Administration (FDA) in 2013 as a supplemental glycemic control therapy in adult T2D patients.

Last year findings for CANVAS were announced at the American Diabetes Association’s 77th Scientific Sessions in San Diego. Canagliflozin reduced the overall risk of CVD by 14% and reduced the risk of hospitalization for heart failure by 33%.

Following CANVAS, Janssen submitted a supplemental New Drug Application to the FDA for a new indication for canagliflozin, specifically for the reduction of the risk of major adverse cardiovascular events in adult patients with T2D.

"The new analysis adds to the body of evidence, which suggests canagliflozin could potentially improve renal outcomes for millions of people with type 2 diabetes and suggests this benefit can be observed in people who have preserved and reduced kidney function," said Bakris.

However, there have been adverse events connected to the drug. A study of the FDA’s adverse event reporting system’s data found that Canagliflozin was found to be involved with 86% of 66 total reports of SGLT2-inhibitor-associated amputations. Additionally, two-thirds of the amputations involving the drug were for patients with no apparent amputation risk factors.

"Although roughly 1 in 3 adults with diabetes develops diabetic kidney disease, there have been no significant advances in treatment for patients," said James F. List, MD, PhD, Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. "We are encouraged that canagliflozin could potentially provide much-needed benefit for those with diabetic kidney disease, and look forward to building further on this insight.”