Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) was the first large, randomized clinical trial of sodium-glucose cotransporter-2 (SGLT2) inhibitors to address the potential benefits and risks of these agents in patients hospitalized with COVID-19. Scientific Sessions attendees will have the first glimpse of a subgroup analysis of patients with type 2 diabetes, who are at higher risk for developing serious complications from COVID-19, including organ failure and death.
Top line results of the trial were released earlier this year showing that SGLT2 inhibitors did not significantly affect organ failure or survival. DARE-19 Principal Investigator Mikhail Kosiborod, MD, will present a subgroup analysis of the results in patients with and without diabetes during the symposium Efficacy and Safety of Dapagliflozin in Patients with and without Type 2 Diabetes Hospitalized with COVID-19—Results from the DARE-19 Global Randomized Controlled Trial. The one-hour session will begin at 2:15 p.m. ET on Sunday, June 27.
“The additional data we are presenting at the ADA Scientific Sessions are of particular interest because just over half of the patients in the trial had type 2 diabetes at baseline,” said Dr. Kosiborod, Vice President of Research at Saint Luke’s Health System and Executive Director of Cardiometabolic Center Alliance. “This is the first time we will be discussing both the efficacy and safety data for this prespecified subgroup analysis. Attendees will find these very relevant to their own clinical practice.”
Because SGLT2 inhibitors have been previously demonstrated to provide organ protection in patients with type 2 diabetes, heart failure, and chronic kidney disease, it was hypothesized they could also be of benefit in the setting of COVID-19. However, some professional groups raised concerns about using SGLT2 inhibitors in this setting due to the potential risk of acute kidney injury and diabetic ketoacidosis, especially in patients with type 2 diabetes.
The investigator-sponsored trial compared dapagliflozin to placebo in 1,250 patients hospitalized for COVID-19 who also had a history of hypertension, atherosclerotic cardiovascular disease, heart failure with either preserved or reduced ejection fraction, type 2 diabetes, or Stage 3/4 chronic kidney disease with an estimated glomerular filtration rate (eGFR) between 25 and 60. Patients received dapagliflozin or placebo for 30 days, plus the usual standard of care in the participating hospital.
DARE-19 was designed in March and April of 2020 and enrolled its first patient on April 22, 2020. Patients were enrolled across 95 centers in seven countries and the last patient was randomized on January 1, 2021.
“We were able to conduct this double-blind, placebo-controlled trial at lightspeed while maintaining the highest standard of methodological rigor,” Dr. Kosiborod said.
The first primary efficacy endpoint was time to first occurrence of new or worsened respiratory, cardiovascular, or kidney organ dysfunction during the 30-day treatment period, or death from any cause through 30 days of follow-up. The second primary endpoint of recovery measured a change in clinical status from early recovery to death. Key secondary outcomes included a composite kidney outcome (acute kidney injury, initiation of renal replacement therapy, or death from any cause) and time to death from any cause.
“DARE-19 provided important data on the potential benefits and risks of using SGLT2 inhibitors to treat hospitalized patients with COVID-19,” Dr. Kosiborod said. “While the trial did not meet statistical significance for the primary endpoints, the details of the efficacy results are very interesting and will undoubtedly inform future clinical science. The safety results are of immediate clinical relevance, especially given prior recommendations from several expert groups to stop these medications in patients hospitalized with COVID-19, even if they have established indications for this class, such as type 2 diabetes and heart failure.”