Compared with placebo, dapagliflozin did not significantly reduce the risk of organ failure or death or improve recovery in patients hospitalized with COVID-19 who were at high risk of developing serious complications, according to findings from the DARE-19 trial presented May 16 during ACC.21. While researchers acknowledged the results were not statistically significant, they did note numerically fewer patients treated with dapagliflozin experienced serious adverse events and that the SGLT2 inhibitor was well tolerated, with numerically fewer serious adverse events than placebo.

The trial enrolled 1,250 patients admitted with COVID-19 at 95 sites in the U.S., Brazil, Mexico, Argentina, India, Canada and the U.K. between April 2020 and January 2021. Patients, who also had risk factors for developing serious complications, including high blood pressure, diabetes, atherosclerotic vascular disease, heart failure or chronic kidney disease, were randomized 1-to-1 to dapagliflozin (10 mg) or placebo once daily. Patients started the treatment as soon as possible (and no later than four days following hospital admission) and continued the treatment for a total of 30 days, even if they were discharged from the hospital.

Overall results found, at 30 days, the primary endpoint of organ failure or death occurred in 11.2% of patients who were treated with dapagliflozin and 13.8% of patients treated with placebo. Altogether, 6.6% of patients in the dapagliflozin group died during study follow-up vs. 8.6% in the placebo group. The second primary endpoint of recovery, driven mostly by time to hospital discharge, was similar between patients taking dapagliflozin and placebo. Of importance, dapagliflozin was well-tolerated, with no new safety issues identified.

According to Mikhail Kosiborod, MD, FACC, the study's principal investigator, for every component of organ failure or death endpoint – respiratory, cardiac, kidney failure or death from any cause – the results appeared to be directionally favorable for dapagliflozin as compared to placebo; however, because they did not reach statistical significance, further study is needed. "Our study generates a hypothesis that dapagliflozin may offer organ protection in acutely ill patients who are hospitalized with COVID-19, but we were not able to prove this beyond a reasonable doubt because patient outcomes rapidly improved during the study period, making it much harder to accrue enough events and reach statistical certainty," he said.

Looking ahead, Kosiborod said the "findings show that dapagliflozin is well-tolerated in patients hospitalized with COVID-19, with no new safety issues being observed" and suggests "this should have implications for clinical practice given that the results do not support discontinuation of SGLT2 inhibitors in this setting, as long as patients are monitored." He goes on to add that the study opens the door to asking additional questions. "The idea for DARE-19 was quite unorthodox when we started – everyone was concentrating on antivirals and anti-inflammatory drugs, so it is fascinating to hypothesize that SGLT2 inhibitors may provide organ protection in acute illness," he said. "This should inform future clinical science and hopefully lead to further investigations."

Clinical Topics: COVID-19 Hub, Diabetes and Cardiometabolic Disease, Dyslipidemia, Geriatric Cardiology, Prevention

Keywords: ACC Annual Scientific Session, ACC21, Metabolic Syndrome, Dyslipidemias, Geriatrics, Primary Prevention, COVID-19, SARS-CoV-2

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