Full results from the cardiovascular outcomes trial for dapagliflozin (Farxiga) will be presented at the American Heart Association annual meeting in November.
The diabetes drug dapagliflozin (Farxiga, AstraZeneca) did not increase the the risk of major cardiovascular (CV) events and produced benefits for heart failure, according to topline results released early today from a 17,000-patient CV outcomes trial.
Dapagliflozin is the last of the first wave of sodium glucose cotransporter 2 (SGLT2) inhibitors to show a CV benefit, adding to the evidence that this is a class effect for these type 2 diabetes drugs, which reached the US market 5 years ago. Competitor empagliflozin (Jardiance, Boehringer-Ingelheim/Lilly) was the first SGLT2 inhibitor to show a CV benefit in 2015.
Full results from the trial, called DECLARE-TIMI 58, will be presented November 10 at the American Heart Association annual meeting in Chicago, according to statement from the company. The trial took place over 5 years involving patients in 33 countries who had T2D with either established CV disease or multiple CV risk factors.
According to the statement from AstraZeneca, dapagliflozin met its primary endpoint, which was to show that the drug did not cause any adverse CV events. Proving safety was the reason that the FDA began requiring CV outcomes trials a decade ago.
In addition, dapagliflozin achieved a statistically significant reduction in a composite endpoint of hospitalization for heart failure or CV death, 1 of 2 primary efficacy endpoints. The statement also said that fewer events were seen for the other primary efficacy endpoint but this did not reach statistical significance.
Data from DECLARE-TIMI 58 confirmed the well-established safety profile of FARXIGA, said Elisabeth Björk, vice president, head of cardiovascular, renal and metabolism, Global Medicines Development at AstraZeneca.
“FARXIGA has achieved a statistically-significant and clinically-important reduction in hospitalization for heart failure or CV death in a broad range of patients with type 2 diabetes and cardiovascular risk,” she said in a statement. “The results from this landmark trial are especially important since heart failure is an early and frequent complication of diabetes and associated with hospitalizations that result in a considerable societal and economic burden.”
The results align with findings from a large international claims-based study, CVD-REAL, which AstraZeneca has sponsored. That study culls data from the United States, Canada, and multiple countries in Europe and Asia to track real-world outcomes of SGLT2 inhibitors as a class. Data presented at the American College of Cardiology the past 2 years show that the drugs prevent hospitalization for heart failure and CV death across a range of populations.
While CV outcomes trials have unexpectedly shown benefits when they were initially designed to show only that drugs did not cause heart attacks and strokes, not everyone believes they are worth the high cost. The FDA has set a 2-day meeting next month (October 24-25) to revisit the value of these large, multinational trials that became required in the wake over concerns about rosiglitazone in the mid-2000s.