AstraZeneca presented detailed results from the DECLARE-TIMI 58 study at the American Heart Association (AHA) conference showing that Farxiga (dapagliflozin) met the co-primary endpoint of significantly reducing a composite of hospitalisation for heart failure (hHF) or cardiovascular (CV) death versus placebo by 17 percent in patients with type 2 diabetes at risk of CV events. In regards to the other primary efficacy endpoint, AstraZeneca noted that there were fewer major adverse CV events (MACE) observed with the SGLT2 inhibitor versus placebo, at rates of 8.8 percent and 9.4 percent, respectively, but this did not reach statistical significance.

DECLARE-TIMI 58, whose results were simultaneously published in the NEJM, involved 17 160 patients with type 2 diabetes who had or were at risk for atherosclerotic CV disease, and who were randomly assigned to treatment with Farxiga or placebo. The authors noted that thetrial included 10 186 patients without atherosclerotic CV disease, who were followed for a median of 4.2 years. The primary safety outcome was a composite of MACE, defined as CV death, myocardial infarction, or ischaemic stroke. The primary efficacy outcomes were MACE and a composite of cardiovascular death or hHF, while secondary efficacy goals were a renal composite and death from any cause.

According to AstraZeneca, the decrease in hHF or CV death was "consistent across the entire population, which included those with CV risk factors and those with established CV disease." The company also stated that although secondary endpoints were "only nominally significant," rates of new or worsening nephropathy were 4.3 percent and 5.6 percent, respectively, for the Farxiga and placebo groups, translating to a reduction of 24 percent. Meanwhile, the rates of all-cause mortality events in the Farxiga and placebo arms were 6.2 percent and 6.6 percent, respectively. 

Regarding safety, AstraZeneca said there was "no imbalance" between Farxiga and placebo in terms of amputations, fractures, bladder cancer or Fournier's gangrene. In August, the FDA issued a warning about a link between SGLT2 inhibitors and Fournier's gangrene. However, AstraZeneca reported one case of Fournier's gangrene among Farxiga-treated patients in the DECLARE-TIMI 58 trial, versus five cases for placebo. The company also said that while rates of diabetic ketoacidosis and genital infections were higher in the Farxiga group, the incidences of these events were rare. 

Elizabeth Bjork, AstraZeneca's head of global medicines development, noted that patients who are at lower risk of CV failure and death "are the kinds of patients that primary-care physicians are seeing every day," and that "this should really open up [Farxiga] usage in a broad population." 

Farxiga, which was cleared by the FDA in 2014 to improve glycaemic control in adults with type 2 diabetes, is not currently indicated to reduce the risk of CV events or hHF. AstraZeneca is expected to pursue US approval of the drug for use in patients with type 1 diabetes later this year, with further regulatory decisions expected in Europe and Japan in 2019. 

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