Researchers from the World Health Organization (WHO) Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group analysed data from three clinical trials, including RECOVERY, to assess whether or not SGLT2 inhibitors such as empagliflozin could improve chances of survival for people in hospital with COVID-19. In accordance with findings previously published by RECOVERY, the study found that SGLT2 inhibitors are not associated with improved survival in patients with COVID-19 when compared with usual care. The results from the study were presented at the European Society of Cardiology Congress 2023 in Amsterdam, Netherlands.
The three trials included in the study were DARE-19, RECOVERY, and ACTIV-4a. The three trials included data on a combined total of 6,096 participants, with 3,025 participants receiving an SGLT-2 inhibitor and 3,071 receiving usual care alone. The primary outcome of this evaluation measured how many patients died within 28 days. The study found that patients who received an SGLT2 inhibitor had an absolute mortality risk of 11.7% when compared with an assumed mortality risk of 12.4% for patients who received usual care or placebo.
Dr Mikhail Kosiborod of Saint Luke's Mid America Heart Institute, Principal Investigator of the DARE-19 and ACTIV-4A trials, and presenting author, said ‘In this prospective meta-analysis of randomised clinical controlled trials evaluating over 6,000 patients hospitalised with COVID-19, we found no strong evidence that administration of SGLT2 inhibitors, compared with usual care or placebo, reduces 28-day all-cause mortality, or improves other pre-specified efficacy outcomes.
‘These findings do not support the use of SGLT2 inhibitors as standard care in this clinical setting. No safety signals were observed with the use of SGLT2 inhibitors in this patient population, and their routine discontinuation during acute illness for patients that receive them for other indications such as heart failure, chronic kidney disease, or type 2 diabetes does not appear to be warranted.’
Richard Haynes, Professor of Renal Medicine and Clinical Trials at Oxford Population Health and the coordinator of the RECOVERY trial, said ‘The result of this meta-analysis confirms and extends earlier findings and provides greater certainty that, while it is not an effective treatment for COVID-19, empagliflozin can be used safely in patients admitted to hospital. We remain enormously grateful to RECOVERY participants, the clinicians involved in their care, and the trial teams for their enormous contribution towards finding effective treatments and improving the chances of survival for patients around the world.’
The RECOVERY trial is continuing to evaluate sotrovimab, a monoclonal antibody treatment, and higher dose corticosteroids in patients who require ventilatory support.