Examining the Potential Benefits of Canagliflozin for Patients with Diabetes

For the 30 million Americans who have diabetes mellitus — including the more than 95 percent with type 2 diabetes —  lifestyle changes, technological advances, and new medical therapies promise to lessen their risk of developing some of the dire outcomes associated with their disease.

In a study of more than 10,000 patients with type 2 diabetes, the drug canagliflozin was shown to reduce adverse outcomes involving the cardiovascular system – death from cardiovascular disease, nonfatal heart attack, or nonfatal stroke – by 14 percent compared to placebo. The study was called the CANVAS Program (Canagliflozin Cardiovascular Assessment Study), and it planned in advance to examine subsets of its patient population to discern whether there were additional benefits of canagliflozin in certain groups of patients.

The first such sub-study to be reported is a comparison of patients enrolled in CANVAS who had never had adverse cardiovascular events (the primary prevention group) versus patients who had experienced such adverse events (the secondary prevention group). Led by Stanford professor Kenneth Mahaffey, MD, the results of the study were presented yesterday at the American Heart Association meeting in Anaheim, California. They also appear in the journal Circulation.

Among the 10,142 CANVAS patients enrolled at 667 centers in 30 countries, 34 percent fit into the primary prevention group and the remaining 66 percent had had prior adverse events and comprised the secondary prevention group. All patients in both groups were randomly assigned to receive either a placebo or canagliflozin. The two groups were then followed for an average of 188 weeks to determine how often the primary endpoint of death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke occurred. Secondary endpoints that were also examined in the substudy were hospitalization for heart failure and evidence of adverse kidney outcomes.

Canagliflozin reduced adverse cardiovascular and renal outcomes in the overall population with likely similar reductions in the secondary and primary prevention groups. The research group also looked at lower extremity amputations and found them to occur more commonly among patients randomized to canagliflozin than to placebo.

Patients in the primary prevention group had fewer adverse outcomes than those in the secondary prevention group, as the latter group experienced more deaths from cardiovascular causes, more nonfatal heart attacks, and more nonfatal strokes than the primary prevention group. Similarly, for heart failure hospitalizations and adverse kidney outcomes, the primary prevention group did better.

Because patients with type 2 diabetes mellitus have a greater risk of adverse cardiovascular and renal events than the general population, they require therapies that will help them manage their disease while reducing their risks. The researchers said that canagliflozin, which appears to be such a therapy, will undergo more study to further delineate its benefits in patients with diabetes.