Dapagliflozin treatment for patients with cardiometabolic risk factors acutely hospitalized with COVID-19 is well tolerated but does not significantly improve kidney outcomes regardless of baseline kidney function, according to the findings from a secondary analysis of the DARE-19 trial, which confirm those of the first analysis.
The secondary analysis focused on the effect of dapagliflozin in patients with and without a baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Results showed that dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, had no significant effect on the likelihood of kidney dysfunction or recovery, Hiddo J.L. Heerspink, PhD, PharmD, of the University of Groningen in The Netherlands, and colleagues reported in the Clinical Journal of the American Society of Nephrology. In addition, dapagliflozin did not significantly increase the risk for acute kidney injury in either subgroup.
The DARE-19 (Dapagliflozin in Respiratory Failure in Patients with COVID-19) trial was the largest clinical trial to date looking at the initiation of an SGLT2 inhibitor in patients hospitalized with acute infectious illness and at high risk for complications, Dr Heerspink’s team noted. The observation that dapagliflozin was well tolerated even among patients with an eGFR less than 60 ml/min/1.73 m2 suggests “that routine discontinuation of SGLT2 inhibitors in this clinical setting may not be necessary as long as patients are adequately monitored,” the authors wrote.
For the trial, investigators randomly assigned 1250 patients who were hospitalized with COVID-19 and cardiometabolic risk factors to receive dapaglifozin or placebo. Of these patients, 231 (18%) had an eGFR less than 60 mL/min/1.73 m2. The follow-up duration was 30 days. The study had dual primary outcomes: prevention and recovery.
The prevention outcome was a composite of time to new or worsened kidney, cardiovascular, or respiratory dysfunction during the index hospitalization, or death from any cause during the 30-day treatment period. Investigators defined worsened kidney function as doubling of serum creatinine or initiation of kidney replacement therapy during the index hospitalization.
The recovery outcome was a change in clinical status by day 30. It was a hierarchical composite end point whereby patients were ranked according to severity and timing of events during the 30-day treatment period. These events included organ dysfunction during the index hospitalization, supplemental oxygen requirement for patients hospitalized at day 30 without organ dysfunction, and hospital discharge before day 30.
Heerspink HJL, Furtado RHM, Berwanger O, et al. Dapagliflozin and kidney outcomes in hospitalized patients with COVID-19 infection. An analysis of the DARE-19 randomized clinical trial. Clin J Am Soc Nephrol. Published online April 28, 2022. doi:10.2215/CJN.14231021