The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial has demonstrated that empagliflozin does not provide any benefit for patients hospitalised with COVID-19. The results of the empagliflozin evaluation have been published on medRxiv and submitted to a leading peer-reviewed medical journal.
The RECOVERY trial is the world’s largest randomised clinical trial of potential treatments for patients hospitalised with COVID-19. The RECOVERY trial assessed the effects of empagliflozin, a routine treatment for type 2 diabetes that has also been shown to have benefits for patients with chronic kidney disease or heart failure. It had been proposed that the drug may protect against organ damage and improve the chance of survival for patients with COVID-19.
Between July 2021 and March 2023, 4,263 patients across six countries were included in the empagliflozin evaluation with 2,107 participants randomly allocated to receive empagliflozin in addition to usual care and 2,156 allocated to usual care alone. Patients who were allocated to the empagliflozin group received 10mg of empagliflozin orally for 28 days or until discharge from hospital, whichever was sooner.
The primary outcome measure of the evaluation was death from any cause within 28 days of randomisation.
The secondary outcomes were: time to discharge from hospital, and, among patients not on invasive mechanical ventilation at randomisation, invasive mechanical ventilation (including extra-corporal membrane oxygenation) or death.
Key findings
- At 28 days after randomisation, there was no evidence that treatment with empagliflozin reduced mortality or improved other clinical outcomes.
- There was no significant difference in the primary outcome of death within 28 days in either group (14% in the empagliflozin group compared with 14% in the usual care alone group).
- The median time to discharge for both groups was eight days for both groups and there was no significant difference in the probability of being discharged alive within 28 days (79% in the empagliflozin group compared with 78% in the usual care alone group).
- In patients who were not receiving invasive mechanical ventilation at randomisation, the number of patients who either needed to receive invasive mechanical ventilation or died within 28 days was similar for both groups (16% in the empagliflozin group compared with 17% in the usual care alone group).
Professor Sir Peter Horby, from the Nuffield Department of Medicine at the University of Oxford, UK, and Joint Chief Investigator of the RECOVERY trial, said ‘A previous clinical trial had suggested that similar drugs to empagliflozin may benefit patients hospitalised with COVID-19 but was not definitive. With the help of patients and clinicians around the world we now know that empagliflozin has no meaningful benefits for this patient group.’
Professor Sir Martin Landray, Professor of Medicine and Epidemiology at Oxford Population Health and Joint Chief Investigator, said ‘The reason that clinical trials such as RECOVERY are so important is that they can properly assess the effects of promising treatments and inform how to treat future patients. In this case, we now know that empagliflozin is not an effective treatment for COVID-19. We are grateful to the thousands of medical staff and patients who have contributed to the RECOVERY trial, helping to find better treatments for patients all around the world.’
The RECOVERY trial is supported by grants to the University of Oxford from the National Institute for Health and Care Research, UK Research and Innovation, and Wellcome. The decision to add empagliflozin to the trial was made by the University of Oxford researchers and Trial Steering Committee leading the trial in conjunction with the Chief Medical Officer, following a recommendation by the UK COVID-19 Therapeutics Advisory Panel. Boehringer-Ingelheim supplied empagliflozin free of charge for use in the RECOVERY trial outside the UK.
Update
The peer-reviewed paper, Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, was published in The Lancet Diabetes & Endocrinology on 18 October 2023.