The study looked at dapagliflozin's benefits in the acute illness setting, specifically organ protection, according to Mikhail N. Kosiborod, MD, vice president of Research at Saint Luke's Health System.
Previous trials of sodium glucose co-transporter 2inhibitors have shown dapagliflozin’s protective effects in the chronic care setting. We looked at its benefits in the acute illness setting, specifically organ protection, noted Mikhail N. Kosiborod, MD,cardiologist, vice president of Research at Saint Luke's Health System, director of Cardiometabolic Research and co-director of the Saint Luke’s Michael & Marlys Haverty Cardiometabolic Center of Excellence at Saint Luke's Mid America Heart Institute, and professor of medicine at the University of Missouri-Kansas City.
Kosiborod’s session, “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 on day 2 of ACC.21.
Can you discuss the purpose of the DARE-19 trial and the main outcomes?
DARE-19 is a trial that's evaluating dapagliflozin as a potential treatment for patients hospitalized with COVID-19 who have cardiometabolic risk factors. We realized very early in the course of the pandemic that patients that have cardiometabolic comorbidities—like type 2 diabetes, for example; heart failure, atherosclerotic cardiovascular disease; chronic kidney disease—are also the patients that have the highest risk of developing complications, or even dying, from COVID-19 in case they're infected.
We knew once the pandemic started about a year ago that if you are admitted to a hospital, if you are sick enough to be in the hospital with COVID-19 and you have one of these risk factors, your outcomes tend to be much worse than if you don't have to be hospitalized or even if you're hospitalized but don't have those risk factors. We also knew from previous trials of SGLT2 [sodium glucose co-transporter 2] inhibitors, including dapagliflozin, that these medications can provide organ protection in other chronic care settings and chronic conditions, like heart failure and diabetes, atherosclerotic cardiovascular disease, and chronic kidney disease.
And we realized also during the early part of the pandemic that COVID-19 is not just a respiratory illness, but it's actually an illness that is systemic—it affects multiple organ systems, including the heart and kidneys—so because of the cardio and natural protection we observed with SGLT2 inhibitors in previous clinical trials under more chronic stable conditions, we hypothesized that it may actually provide organ protection also in the setting of acute illness, like COVID-19. It's a lot of mechanistic data also suggesting that some of the key pathophysiologic processes that are dysregulated in the setting of COVID-19 are also the same processes that SGLT2 inhibitors might have a favorable impact on.
So that ultimately led us to propose that dapagliflozin, which is an SGLT2 inhibitor, may provide organ protection and prevent the risk of organ failure or death, or improve time to clinical recovery, in patients that have those cardiometabolic conditions and are hospitalized with COVID-19.
What are the risks and benefits of dapagliflozin in COVID-19 long-haulers?
The DARE-19 trial evaluated dapagliflozin over a treatment period of 30 days. Now, we did build in an additional 60-day observational period after discontinuation of study medication at 30 days, so the total duration was actually 90 days. But the data that have we presented to the American College of Cardiology is the prespecified primary analysis for both efficacy and safety, which is the data during the 30-day treatment period. We do not yet have data available for this observational, additional 60-day follow-up after discontinuation of study medication. Those data will be available at a later time point.
With that acknowledged, I think it's difficult to say whether SGLT2 inhibitors at this point in time would have an effect on longer-term symptoms of COVID-19. It's certainly possible that if you have an agent that's efficacious in preventing acute complications, that may have a longer-term effect. While we had numerically fewer events of organ failure or death in the dapagliflozin group as compared to the placebo group, this did not reach statistical significance. It's a more of a hypothesis-generating trial in such regards, rather than hypothesis-proving trial, so I don't think we're going to get definitive answers on the potential role of SGLT2 inhibitors on long-term COVID effects after the acute phase of the illness has resolved, unless we do dedicated studies to specifically address that question.