The DARE-19 clinical trial explores the use of SGLT2 inhibitors for patients with hypertension, cardiovascular disease, heart failure, type 2 diabetes, or chronic kidney disease, and COVID-19.
A recent study found that dapagliflozin (Farxiga; AstraZeneca), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, was well-tolerated in hospitalized patients with COVID-19, and participating patients had fewer serious adverse events than those taking placebo. Results of the DARE-19 trial (NCT04350593) were presented Sunday during the virtual 81st Scientific Sessions of the American Diabetes Association (ADA).1
According to the ADA, DARE-19 is the first large randomized clinical trial to assess SGLT2 inhibitors, a medication class initially used to help lower blood glucose, in patients with and without type 2 diabetes who are hospitalized with COVID-19. Funded by AstraZeneca, the study found that treatment with dapagliflozin did not achieve statistically significant reduction in organ failure or death, nor did it significantly improve clinical recovery, compared with placebo. However, fewer patients treated with dapagliflozin experienced organ failure or death compared to placebo (11.2% vs 13.8%, respectively).1
“Previously, there were some concerns with using SGLT2 inhibitors in COVID-19 patients due to the potential risk for acute kidney injury and diabetic ketoacidosis. However, our results show dapagliflozin is well tolerated, with no new safety concerns,” said the study’s lead investigator Mikhail Kosiborod, cardiologist and vice president for research at Saint Luke's Health System; and professor of medicine, University of Missouri-Kansas City, in a press release. “We believe that our findings do not support routine discontinuation of SGLT2 inhibitors in patients hospitalized with COVID-19 that have other indications for these agents, such as type 2 diabetes, heart failure and chronic kidney disease (CKD), as long as patients are monitored.”
Patients with cardiometabolic risk factors, including type 2 diabetes, are at higher risk for developing serious COVID-19-related complications, such as organ failure and death. According to the ADA, Americans with diabetes and other related underlying health conditions are hospitalized 6 times more often and are 12 times more likely to die of COVID-19 than those without diabetes. Previous studies have shown SGLT2 inhibitors provide organ protection in patients with type 2 diabetes, heart failure, and chronic kidney disease.1
Dapagliflozin is indicated to reduce the risk of sustained glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular (CV) death, and hospitalization for heart failure in adult patients with CKD at risk of progression, according to AstraZeneca. The drug is also indicated to reduce the risk of CV death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction, and to reduce the risk of hospitalization in adults with type 2 diabetes and either established CV disease or multiple CV risk factors. Dapagliflozin is used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes, and is not recommended for patients with type 1 diabetes.2
DARE-19 compared dapagliflozin to placebo in 1250 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 to 4 chronic kidney disease with estimated eGFR between 25 and 60. Patients were recruited across 95 centers in seven countries between April 2020 and January 2021. Approximately half of the patients had a history of type 2 diabetes. Patients received dapagliflozin or placebo for 30 days in addition to the standard of care for COVID-19 in the participating hospital.1
According to the investigators, future trials are needed to further evaluate the possible effects of dapagliflozin on the risk of organ failure or death in patients hospitalized with COVID-19. They also noted that DARE-19 has important implications for future research, as it raises a hypothesis that SGLT2 inhibitors may offer organ protection in other types of acute illness such as sepsis, which should be explored in future studies.1