Results are based on the DECLARE-TIMI 58 cardiovascular outcomes trial, presented last year at the American Heart Association Scientific Sessions.
The FDA today approved AstraZeneca’s dapagliflozin (Farxiga) to reduce the risk of hospitalization for heart failure for patients with type 2 diabetes (T2D) and established cardiovascular disease or multiple cardiovascular risk factors.
The approval comes almost a year after presentation of results from the 17,000-patient DECLARE-TIMI 58 cardiovascular outcomes trial (CVOT), which showed that the sodium glucose co-transporter 2 (SGLT2) inhibitor significantly reduced hospitalization for heart failure and appeared to slow the loss of kidney function.
SGLT2 inhibitors work differently than other drugs for T2D by targeting a protein that normally causes the body to take excess glucose back up into the body; instead, excess glucose is expelled through the urine, thus keeping glycated hemoglobin in check. Besides its ability to prevent heart failure, the drug class has been shown to prevent renal decline.
Notably, AstraZeneca was the only manufacturer among the makers of the 3 major SGLT2 inhibitors sold in the United States to come away from a CVOT having met a primary endpoint that included heart failure. Researchers added a second composite primary endpoint of cardiovascular death and hospitalization for heart failure after the 2015 results for empagliflozin showed a 38% reduction in cardiovascular death and a 35% reduction in hospitalization for heart failure.
Results from DECLARE-TIMI were presented in November 2018 at the American Heart Association Scientific Sessions and published in the New England Journal of Medicine in January 2019.1
While results of SGLT2s on heart failure have been reported in other outcomes trials and in real-world studies—including a large study sponsored by AstraZeneca—the decision to expand DECLARE-TIMI 58 means that dapagliflozin is first to the finish line with a specific indication for reducing the risk of hospitalization for heart failure in certain patients with T2D.
Competitors empagliflozin (Jardiance) and canagliflozin (Invokana) have different cardiovascular indications, for reducing the risk of cardiovascular events. FDA has granted dapagliflozin Fast Track designation for an indication of reducing the risk of cardiovascular death for patients with heart failure with reduced ejection fraction or preserved ejection fraction, as well as Fast Track designation for a designation to prevent progression of renal failure, based on separate ongoing trials.
“DECLARE-TIMI 58 is a landmark trial, offering compelling evidence that dapagliflozin can reduce the risk of heart failure in patients living with type 2 diabetes with multiple risk factors for or established cardiovascular disease,” said Stephen Wiviott, MD, of Brigham and Women’s Hospital and Harvard Medical School, who led the study, in a statement.
“These data could help change the way we approach diabetes management—going beyond a singular focus on glucose control to help address the risk of heart failure in a diverse population of patients,” he said.
Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357. doi: 10.1056/NEJMoa1812389.