For the first time, an oral diabetes therapy has been approved by the FDA to reduce the risk of major adverse cardiovascular events.

Janssen Pharmaceutical Companies of Johnson & Johnson announced FDA approval of canagliflozin, marketed as Invokana, to reduce the risk of heart attack, stroke or death due to a cardiovascular cause in adults with type 2 diabetes (T2D) who have established CV disease.

The approval was based on results of the CANVAS (CANagliflozin cardioVascular Assessment Study) Program, which evaluated the effect of canagliflozin, a sodium-glucose cotransporter-2 inhibitor, on CV risk in a broad population of more than 10,000 adults with T2D.

​White tablets. Source: Getty

"This FDA approval makes [Canagliflozin] the only oral type 2 diabetes treatment indicated to reduce the risk of heart attack, stroke or CV death. It is an important step forward for patients and the physicians who treat them," explained James List, MD, PhD, Global Therapeutic Area Head, Cardiovascular & Metabolism, at Janssen Research & Development."Not only does [Canagliflozin] enable patients to control their diabetes symptoms by lowering their A1C levels, but it now also helps protect them from potentially devastating cardiovascular events."

Type 2 diabetes mellitus is associated with a substantial risk of cardiovascular and renal disease, and the FDA action is in line with recent clinical guideline updates. The American Diabetes Association recommends use of a SGLT2 inhibitor for patients with T2D and clinical CV disease, while the American Association of Clinical Endocrinologists advises that, for  appropriate patients, canagliflozin has been shown to reduce major adverse CV events.

"Americans living with type 2 diabetes are two to three times more likely to die from heart disease than adults without diabetes," pointed out Ralph DeFronzo, MD, professor of medicine and chief of the Division of Diabetes at University of Texas, Health Diabetes Center, San Antonio. "With this approval, [Canagliflozin] now plays an even more important role in the overall treatment mix with its demonstrated ability to reduce the risk of potentially devastating cardiovascular events."

Canagliflozin reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. A report last year in the New England Journal of Medicine confirmed the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes.

The CANVAS Program integrated data from two trials involving 10,142 participants with type 2 diabetes and high cardiovascular risk. In each trial, participants were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The international researchers defined the primary endpoint as a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

Results indicated that the rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority).

“Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77),” researchers wrote.

“In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal,” study authors concluded.

This new indication also applies to the fixed-dose combinations of canagliflozin/metformin HCl tablets and canagliflozin/metformin HCl extended-release tablets.