The SGLT2 inhibitor, on October 21, 2019 was granted a label expansion from FDA for the prevention of hospitalization for heart failure in patients with T2D.
The FDA on October 21, 2019, approved a label expansion for dapagliflozin (FARXIGA, AstraZeneca) to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or multiple cardiovascular (CV) risk factors. The new indication was announced in a press release from AstraZeneca.
The approval is based on results from the DECLARE-TIMI 58 CV outcomes trial (CVOT), the largest sodium-glucose cotransporter 2 (SGLT2) inhibitor CVOT conducted to date to evaluate T2D patients with multiple CV risk factors or established CV disease. The full results of DECLARE-TIMI 58 were published in the NEJM in January, 2019.
“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,” Dr Stephen Wiviott of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in the AstraZeneca press release. “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.” Dr Wiviott is a senior investigator with the TIMI study group and co-principal investigator of the trial.
Largest CVOT to date
The phase 3 randomized, double-blind, placebo-controlled DECLARE-TIMI 58 trial evaluated the effect of dapagliflozin vs placebo on cardiovascular events in adults with T2D and established CVD or with multiple CV risk factors. The study included 17 160 patients, including more than 10 000 without established CV disease, who were followed for a median of 4.2 years. There were 882 study sites across 33 countries.
Treatment with dapagliflozin significantly reduced the risk of the primary composite endpoint of hospitalization for heart failure or CV death vs placebo by 17% (4.9% vs 5.8%), this finding driven largely by a significant 27% reduction in the risk of hospitalization for heart failure (2.5% vs 3.3%).
Study authors note in their discussion of the DECLARE-TIMI 58 results that current international guidelines for management of diabetes recommend SGLT2 inhibitors in patients with T2D and established atherosclerotic CVD (ASCVD). These new data suggest that in patients without confirmed ASCVD, SGLT2 inhibition can prevent serious clinical events, particularly hospitalization for heart failure, and possibly reduce the likelihood of progression of renal disease.
According to a press announcement from AstraZeneca, the most common adverse events during the study associated with dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).
The approval follows the marketing authorization in the EU and regulatory review is underway in China with a decision anticipated in the first half of 2020. Furthermore, the FDA recently granted fast-track designation for the development of Farxiga to reduce the risk of CV death, or the worsening of heart failure with reduced ejection fraction or preserved ejection fracture based on the Phase III trials, DAPA-HF and DELIVER.
FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus and to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and established cardiovascular disease or multiple cardiovascular risk factors.