Strong Cardio Safety Data for SGLT2 Inhibitor
These data, from the integrated analysis of the CANVAS and CANVAS-R trials, demonstrated the CV safety of canagliflozin (P
Canagliflozin (Invokana, Johnson & Johnson) achieved a 14% reduction in the risk of cardiovascular (CV) mortality, nonfatal myocardial infarction (MI) or nonfatal stroke, according to clinical trial results presented at the American Diabetes Association 77th Scientific Sessions meeting held in San Diego this week, and also published in the New England Journal of Medicine.
These data, from the integrated analysis of the CANVAS and CANVAS-R trials, demonstrated the CV safety of canagliflozin (P<.0001 for non-inferiority) and superiority compared to placebo (P=.0158). Each component evenly contributed to this risk reduction, including nonfatal MI by 15% (HR: 0.85; 95% CI: 0.69 to 1.05), CV death by 13% (HR: 0.87; 95% CI: 0.72 to 1.06), and nonfatal stroke by 10% (HR: 0.90; 95% CI: 0.71 to 1.15). These outcomes were broadly consistent across various patient subgroups and across the individual components of the primary endpoint.
In addition, canagliflozin, which is a sodium glucose cotransporter-2 (SGLT2) inhibitor, showed potential renal protective effects, delaying progression of albuminuria and reducing the risk of clinically important renal composite outcomes (such as renal death, renal replacement therapy, and 40% reduction of eGFR) by 40% (HR: 0.60; 95% CI: 0.47 to 0.77).
Overall adverse events seen in the CANVAS Program were consistent with previous findings, including an increased risk of amputation with canagliflozin. There was an increased risk of amputation (6.3 vs. 3.4/1000 patient-years) corresponding to a hazard ratio (HR) of 1.97. The highest absolute risk of amputation occurred in patients with a prior history of amputation or peripheral vascular disease, but the relative risk for amputation with canagliflozin was comparable across these subgroups. These findings have been shared by the US FDA and will be reflected in the U.S. Prescribing Information for canagliflozin.
The CANVAS Program is the largest completed CV outcomes program of any SGLT2 inhibitor to date, with a total of 10,142 patients — 4,330 patients in CANVAS and 5,812 patients in CANVAS-R.
Since 2013, when the FDA approved canagliflozin as a first-in-class medication for treating diabetes, at least 5 new medications and combination treatments in this class have gained FDA approval. Each SGLT2 inhibitor differs slightly from the others.