FDA Approves Canagliflozin for Type 2 Diabetes Patients with Cardiovascular Disease

Officials with the US FDA have approved canagliflozin (Invokana, Janssen) to reduce the risk of major adverse cardiovascular (CV) events, including heart attack, stroke or death due to a cardiovascular cause in adults with type 2 diabetes (T2D) who have established CV disease.

The CANVAS (CANagliflozin cardioVascular Assessment Study) Program evaluated canagliflozin's effect on CV risk in a population of more than 10,000 adults with T2D who had established CV disease (65%) or were at risk for cardiovascular disease with 2 or more risk factors (35%). The study researchers concluded that treatment with canagliflozin as compared with placebo in addition to standard of care reduced the combined risk of heart attack, stroke and CV death by 14% (events occurred in 26.9 vs. 31.5 participants, respectively, per 1000 patient-years; HR: 0.86; 95 percent CI: 0.75 to 0.97;

P

<.0001 for non-inferiority and

P

=.0158 for superiority). In patients with established CV disease, treatment reduced the combined risk of heart attack, stroke and CV death by 18% compared to placebo (events occurred in 34.1 vs. 41.3 participants, respectively, per 1000 patient-years; HR: 0.82; 95% CI: 0.72 to 0.95).

Data from the integrated analysis of the CANVAS and CANVAS-R trials, reported at the American Diabetes Association meeting in 2017, suggested an increased risk of below knee lower exteremity amputation with canagliflozin. 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 were then reflected in the US Prescribing Information for canagliflozin.

In the OBSERVE-4D analysis, however, researchers observed no increased risks across the therapy comparisons for BKLE amputations in the general T2D population:

This FDA approval builds on recent consensus reports from the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists (AACE) that support the use of Invokana across a broad range of patients. For patients with T2D and clinical CV disease, the ADA recommends medication management with SGLT2 (sodium-glucose cotransporter-2) inhibitors that specifically have a proven cardiovascular benefit. AACE also notes that for appropriate patients, Invokana has been shown to reduce major adverse CV events.

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

This article was originally published on Pharmacy Times.