Results from the Dapagliflozin in Respiratory Failure in Patients With COVID-19 (DARE-19) trial reported at the Scientific Sessions showed that dapagliflozin does not protect patients hospitalized with COVID-19 against organ failure or death, nor does dapagliflozin improve recovery compared to placebo.

“Treatment with dapagliflozin did not achieve statistical significance and there was no statistical heterogeneity in those with and without diabetes,” said Otávio Berwanger, MD, PhD, Director of the Research Institute HCor, Heart Hospital, São Paulo, Brazil. “Numerically, fewer patients treated with dapagliflozin experienced organ failure and death, a trend seen across all components—respiratory, cardiovascular, kidney complications, and death.”

DARE-19 was the first large, randomized clinical trial of a sodium-glucose cotransporter-2 (SGLT2) inhibitor to address the potential benefits and risks of these agents in patients hospitalized with COVID-19. Top line results of the trial were released earlier this year showing that dapagliflozin did not significantly affect organ failure or survival.

Researchers presented final results of of the trial, including a subgroup analysis of patients with type 2 diabetes, on Sunday, June 27, 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 session can be viewed by registered meeting attendees at ADA2021.org through September 29, 2021. If you haven’t registered for the Virtual 81st Scientific Sessions, register today to access all of the valuable meeting content.

DARE-19 compared a 10 mg daily dose of dapagliflozin to placebo in 1,250 patients at more than 90 centers in seven countries who were hospitalized with confirmed or suspected COVID-19. The trial was launched in March 2020 during the early days of the COVID-19 pandemic.

All patients in DARE-19 had one or more cardiovascular risk factors, such as hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. Early pandemic data showed that COVID-19 patients with cardiometabolic risk factors were at extremely high risk for hospitalization, disease progression, and death.

“When we launched this trial in March 2020, about 15% of COVID-19 patients required hospitalization and at least a third progressed to critical illness requiring ICU-level care,” said principal investigator Mikhail N. Kosiborod, MD, Vice President of Research, Saint Luke’s Health System, and Professor of Medicine, University of Missouri–Kansas City. “Mortality among those ICU-level patients was approaching 50%. Decreasing the severity of COVID illness and preventing complications were critical priorities.”

The initial primary outcome of DARE-19 was prevention of organ failure or all-cause mortality in the 30 days following hospital admission for COVID-19. As clinicians gained experience treating COVID-19 during 2020, mortality rates plummeted from 25% to 30% in March and April to less than 5% in August and September, prompting the addition of a second co-primary outcome of recovery. Treatment with dapagliflozin had no significant effect on discharge, stable disease, or worsening disease, Dr. Berwanger reported.

DARE-19 also demonstrated that concerns over elevated risk for diabetic ketoacidosis (DKA) in hospitalized COVID-19 patients taking dapagliflozin are overstated. The trial protocol required active surveillance for DKA in all patients.

“There was a numerical reduction in DKA and acute kidney injuries in dapagliflozin-treated patients, but this did not achieve statistical significance regardless of diabetes status,” reported Subodh Verma, MD, PhD, FRCSC, Professor of Medicine, University of Toronto, and Canada Research Chair in Cardiovascular Surgery at St. Michael’s Hospital, Toronto.

There were similar numerical improvements in adverse events, serum bicarbonate, hematocrit, estimated glomerular filtration rate, and glucose values with dapagliflozin treatment, but the differences were not statistically significant.

“The overall results of DARE-19 suggest that SGLT2 inhibition may offer organ protection and we need larger trials and other illnesses to investigate the potential,” Dr. Kosiborod said. “The results, by demonstrating the safety of dapagliflozin in patients hospitalized with acute illness, again highlight the value of challenging conventional wisdom and treatment guidelines with carefully constructed clinical trials.”