Dapagliflozin fails to prevent organ damage, death in adults hospitalized with COVID-19
Top-line data from the phase 3 DARE-19 trial show that the SGLT2 inhibitor dapagliflozin failed to prevent organ dysfunction and all-cause mortality among hospitalized patients with COVID-19 at risk for developing serious complications.
In a press release, AstraZeneca and Saint Luke’s Mid America Heart Institute announced that the trial did not achieve statistical significance for the primary endpoint of prevention measuring organ dysfunction and all-cause mortality, and the primary endpoint of recovery measuring a change in clinical status — from early recovery to death — at 30 days. However, researchers noted the trial still yielded important clinical data on the use of SGLT2 inhibitors in adults hospitalized with COVID-19.
“DARE-19 provided important data on the potential benefits and risks of using SGLT2 inhibitors to treat hospitalized patients with COVID-19,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute, professor of medicine at the University of Missouri-Kansas City School of Medicine and a principal investigator for DARE-19, said in a press release. “While the trial did not achieve statistical significance, the findings are very interesting and valuable, and will inform future clinical science. Also, of importance, we learned that dapagliflozin’s well-established safety profile was consistent in DARE-19.”
As Healio previously reported, researchers began recruiting for the global phase 3 trial in April 2020. DARE-19 was the first phase 3 trial to evaluate the safety and efficacy of an SGLT2 inhibitor in patients hospitalized with COVID-19 who also have risk factors for developing serious complications, including hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure or chronic kidney disease. The trial design was supported by extensive data on the protective effect of dapagliflozin (Farxiga, AstraZeneca) among adults with heart failure with reduced ejection fraction, CKD or type 2 diabetes.
In a virtual presentation at the Heart in Diabetes conference in August, Kosiborod said viral replication and spread after COVID-19 infection trigger metabolic derangements that lead to inflammatory “overdrive,” endothelial injury and, ultimately, organ damage leading to complications and death. Data suggest antiviral treatments can work in the early phase of the disease; anti-inflammatory medications show promise during the mid-phase of the disease, he said.
“Prior to the DARE-19 phase 3 trial, there was little data on the use of SGLT2 inhibitors in hospitalized patients with COVID-19, and we have now helped to fill this knowledge gap,”
Mene Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said in the release. “We look forward to the efficacy and safety data being presented in the coming weeks.”
The full DARE-19 trial results will be presented at the American College of Cardiology Scientific Session in May.