DARE-19 Demonstrates Dapagliflozin is Safe for Use, But Ineffective as Treatment for COVID-19

This article was originally published on HCPLive.com.

Dapagliflozin was not associated with significantly reduced risk of organ failure, improved recovery, or death in patients hospitalized with COVID-19, according to findings from a novel assessment of the SGLT-2 inhibitor in treating severe systemic complications arisen from the pandemic virus.

In new findings from the DARE-19 trial, presented at the American College of Cardiology (ACC) 2021 Scientific Sessions this weekend, the AstraZeneca-funded research suggested a unique avenue of treatment for patients with severe COVID-19—though the primary outcome was not achieved.

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Presented by principal investigator Mikhail Kosiborod, MD, of Saint Luke's Mid America Heart Institute, the phase 3 trial sought to interpret dapagliflozin’s benefit in cardiovascular, renal, and respiratory complications or all-cause death in patients acutely ill and hospitalized with COVID-19. They additionally sough a dual primary endpoint of improved recovery in treated patients.

As highlighted by Kosiborod on HCPLive podcast Heart Trials, dapagliflozin and SGLT-2 inhibitors have been associated with improved cardiovascular, glycemic, and renal outcomes in patients with heart disease across multiple phase 3 trials. As such, its potential for treating greater and varied systemic outcomes is considered a worthwhile endeavor by he and his peers.

“They’re not just drugs for diabetes, they’re not just drugs for heart failure, they’re not just drugs for chronic kidney disease,” he explained. “They may actually provide organ protection in a variety of clinical situations.”

Kosiborod and colleagues included 1250 participants admitted to the hospital with COVID-19 from 95 US and international sites, between April 2020 – January 2021. Eligible patients included those with high risk factors for developing severe COVID-19: hypertension, diabetes, atherosclerotic vascular disease, heart failure, or chronic kidney disease.

Patients were randomized 1:1 to once-daily 10 mg dapagliflozin or placebo, with treatment initiation beginning no later than 4 days post-admission and lasting for 30 days.

At the end of treatment, organ failure or death was observed in 11.2% of patients treated with dapagliflozin, versus 13.8% treated with placebo. Death was similarly less prevalent in dapagliflozin patients (6.6%) versus placebo patients (8.6%).

Though dapagliflozin appeared to be beneficial for every iterations of cardiac, respiratory, and kidney failure outcomes versus placebo, the treatment did not reach statistical significance in the primary endpoints.

Patients generally reported tolerance of dapagliflozin, without any new safety outcomes observed in any treated patients.

Additional 90-day follow-up data is being assessed from the DARE-19 population. In the meantime, Kosiborod and colleagues pointed to positive findings including safety in patients with severe COVID-19 treated with dapagliflozin—a notion which earlier in the pandemic was uncertain, and resulted in the discontinuation of SGLT-2 inhibitors among patients with high-risk chronic diseases.

“These were largely theoretical concerns that were based on an appropriate caution, but there wasn’t a lot of data at the time, because of course we didn’t have enough data (on COVID-19),” Kosiborod explained.

Despite falling short of statistical significance, Kosiborod praised the DARE-19 data as “extremely interesting,” and contributing to important new questions in COVID-19 care.

“Every good trial may answer some questions and may ask more questions,” Kosiborod said. “That’s the way clinical science goes—it’s an iterative process.”

The study, "Effects of Dapagliflozin on Prevention of Major Clinical Events and Recovery in Patients with Respiratory Failure due to COVID-19 - Main Results from the DARE-19 Randomized Trial,” was presented at ACC 2021.