Canagliflozin Approved for Type 2 Diabetes & Established Cardiovascular Disease

The US Food and Drug Administration (FDA) has approved Johnson & Johnson’s canagliflozin (INVOKANA) for patients with type 2 diabetes who have established cardiovascular disease in order to reduce the risk of major adverse cardiovascular events, such as heart attack, stroke, or death.

“This FDA approval makes canagliflozin the only oral type 2 diabetes treatment indicated to reduce the risk of heart attack, stroke or cardiovascular death. It is an important step forward for patients and the physicians who treat them,” said James List, MD, PhD, Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC, in a recent statement. “Not only does canagliflozin’s enable patients to control their diabetes symptoms by lowering their A1C levels, but it now also helps protect them from potentially devastating cardiovascular events.”

In a broad population of more than 10,000 adults with type 2 diabetes who had established cardiovascular disease (65%) or were at risk for cardiovascular disease with 2 or more risk factors (35%), the CANVAS (CANagliflozin cardioVascular Assessment Study) Program assessed canagliflozin’s effect on cardiovascular risk as the longest, largest and broadest completed cardiovascular outcomes program of any SGLT2 inhibitor.

Major adverse cardiovascular events (MACE), which included nonfatal heart attack, nonfatal stroke, and cardiovascular death, served as the primary endpoint. The progression of albuminuria, beta-cell function, estimated glomerular filtration rate changes, and urine albumin—to–creatinine ratio served as the secondary endpoint.

In addition to the standard of care, reductions in the combined risk of heart attack, stroke, and cardiovascular death by 14% (events occurred in 26.9 versus 31.5 participants, respectively, per 1000 patient-years; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.75 to 0.97; P<.0001 for non-inferiority and P = .0158 for superiority) were observed in patients treated with canagliflozin compared with placebo.

Additionally, the combined risk of heart attack, stroke and cardiovascular death was reduced by treatment with canagliflozin by 18% compared to placebo in patients with established cardiovascular disease (events occurred in 34.1 versus 41.3 participants, respectively, per 1000 patient-years; HR: 0.82; 95% CI: 0.72 to 0.95).

Observed overall adverse events were generally low in the CANVAS Program and consistent with previous findings. However, a low, but increased risk of below-knee lower extremity amputation was noted. Information regarding renal cell carcinoma from the CANVAS Program was noted by the principal investigator under 'Adverse Reactions'.

“Americans living with type 2 diabetes are 2 to 3 times more likely to die from heart disease than adults without diabetes,” added Ralph DeFronzo, M.D., professor of medicine and chief of the Division of Diabetes at University of Texas, Health Diabetes Center, San Antonio, in a statement. “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 is prescribed to lower blood sugar (glucose) for adults with type 2 diabetes when in combination with diet and exercise. It is not intended for patients with type 1 diabetes or with diabetic ketoacidosis (increased ketones in blood or urine).