From today, empagliflozin – a routine treatment for type 2 diabetes – will be investigated in the Randomised Evaluation of COVid-19 thERapY (RECOVERY) trial. This is the world’s largest clinical trial of treatments for patients hospitalised with COVID-19, taking place in 185 hospitals in the UK, Nepal and Indonesia and with over 41,000 patients recruited so far.
Empagliflozin is regularly used to treat type 2 diabetes, and has also been shown to have benefits for patients with chronic kidney disease or heart failure. The drug works by reversibly blocking the action of a sodium-glucose co-transporter (SGLT) in the kidney. This reduces the amount of glucose absorbed by the body, causing it to be excreted into the urine instead. It is thought that sodium-glucose co-transporters may help stabilise metabolic pathways that become dysregulated during viral infection, reduce inflammation, improve heart and blood vessel function, and increase blood oxygen transport. Together, these actions may protect against organ damage and improve the chance of recovery for patients with COVID-19.
A similar sodium-glucose co-transporter inhibitor, dapagliflozin, was compared to a placebo among 1250 hospitalised COVID-19 patients by the DARE-19 trial. In patients treated with the drug, there was a non-significant reduction in the risk of organ failure or death of one-fifth and there were no major safety concerns with its use.
Professor Sir Peter Horby, from the Nuffield Department of Medicine at the University of Oxford, UK, Co-Chief Investigator of the RECOVERY trial, said ‘The COVID-19 pandemic still has a long way to run, and whilst COVID-19 continues to claim lives, we will continue our quest to find new, affordable treatments that are accessible to all. I’m delighted that we are adding empagliflozin, since this will test a new treatment strategy using a class of drugs that are widely available and relatively inexpensive.’
Professor Sir Martin Landray, from the Nuffield Department of Population Health at the University of Oxford, who co-leads the RECOVERY trial said ‘Empagliflozin and similar SGLT2-inhibitor drugs have been shown to have significant benefits on the heart and kidney in patients with or without diabetes. The recent DARE-19 trial provided encouraging but inconclusive evidence that these drugs may reduce the risk of lung, heart, and kidney damage or death in patients hospitalised with COVID-19. By including empagliflozin in a much larger comparison within the RECOVERY trial, we will be able to determine whether this early promise turns into a reality.’
It is anticipated that at least 2500 patients recruited to the RECOVERY trial will be randomly allocated to receive empagliflozin plus usual standard-of-care, and results will be compared with at least 2500 patients who receive usual standard-of-care on its own. The dosage of empagliflozin used will be a 10mg tablet once daily. The main aim is to assess whether empagliflozin reduces the risk of death among patients admitted to hospital with COVID-19. The trial will also investigate whether the treatment shortens the length of hospital stay or reduces the need for a mechanical ventilator. It is likely to be several months before the results are available.
Sodium-glucose co-transporter inhibitors are not considered to be safe in pregnancy and breastfeeding, so these women will not be included in this comparison.
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.
The other treatments currently being investigated in the RECOVERY trial are:
- baricitinib (an immunomodulatory drug used in rheumatoid arthritis)
- dimethyl fumarate (an immunomodulatory drug used in psoriasis and multiple sclerosis)
- high-dose vs standard corticosteroids.