SGLT-2 inhibitors have demonstrated efficacy in various cardiometabolic conditions, including heart failure, coronary artery disease, chronic kidney disease, and diabetes. Given its favorable profile in various disease states, and the lack of effective therapies for patients hospitalized with COVID-19, it was hypothesized that dapagliflozin could provide organ protection in patients with cardiometabolic risk factors and COVID-19. During today’s Late Breaking Clinical Trials Session at the American College of Cardiology 2021 Scientific Sessions meeting, Dr. Mikhail Kosiborod of Saint Luke’s Mid Americas Hospital system presenting the findings of DARE-19, Dapagliflozin in Respiratory Failure in patients with COVID-19.
This multinational, multicenter randomized control trial enrolled 1250 patients at 95 sites in 7 countries. Patients with strongly suspected or confirmed COVID-19 infection were randomized in a 1:1 fashion to receive either dapagliflozin 10 mg/day or placebo in addition to standard of treatment. The study prespecified dual primary endpoints of prevention (time to first major clinical event, including respiratory , cardiovascular, kidney, or death events), and recovery, a hierarchical ranking of death, organ failure, clinical status if hospitalized at day 30, and time to hospital discharge before day 30.
Enrolled patients had a mean age of 61 years. 50% in either group had diabetes, and 85% had hypertension. One third of patients in either arm were already on ACE-inhibitors or Angiotensin receptor blockers prior to initiation of the study drug.
At thirty days, while dapagliflozin was associated with fever organ dysfunction events, it did not meet statistical significant for the primary outcome of prevention of organ failure, either as a composite or in its components, with an overall event rate of 11.2% compared to 13.8% in the placebo arm (HR 0.80, 95% CI 0.58 -1.1, p = 0.168). Furthermore, it appeared to fare no differently than placebo when assessing the primary outcome of recovery.
Interestingly, dapagliflozin was associated with fewer adverse events when compared to placebo across the board, including acute kidney injury and discontinuation of drugs due to adverse event. This was an especially important finding, as SGLT-2 inhibitors, along with ACE-inhibitors were held by some providers early in the pandemic for safety concerns.
Despite the failure of dapaglifozin to meet statistical significance for its primary endpoints in the DARE-19 trial, this remains the first and largest trial to assess the role of SGLT-2 inhibitors in acute illness, and is to be commended. This study paves the way for future trials to investigate the protective role of SGLT inhibitors in organ dysfunction due to acute illness.