Can Metformin reduce risk of long Covid by 40 per cent? Experts still wary of new study

Results reinforce strength of Metformin

Metformin prevented over 40 per cent of cases of long COVID in the trial with 6.3 per cent (35/564) of participants given Metformin reporting a long COVID diagnosis within 10 months of follow-up, compared to 10.4 per cent (58/562) of those receiving an identical placebo. “This is the first phase 3 randomised controlled trial of a treatment for patients in the community that shows a medication can reduce the risk of long COVID when taken after testing positive for SARS-CoV-2. Our study showed that Metformin, a medication that is safe, low-cost and widely available, substantially reduces the risk of being diagnosed with long COVID if taken when first infected with the Coronavirus. This trial does not indicate whether Metformin would be effective as a treatment for those who already have long COVID,” said first author Dr Carolyn Bramante, University of Minnesota Medical School, US. Experts say that over time, different uses of Metformin have been discovered.

‘Idea not new but the trial is’

This is a drug that has been used for more than 60 years to treat Type 2 diabetes in the early stages. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and according to Dr V Mohan, Chairman and Chief of Diabetology at Dr Mohan’s Diabetes Specialities Centre, Chennai, the idea is not new but the trial is a new one. The logic of using Metformin was based on the findings that it inhibited reproduction of the virus in cell culture and human lung tissue.

“Ever since the Covid pandemic, various studies have looked at which drug would have a better prognosis with COVID 19. Several studies have shown that those on Metformin did better, whereas those on stronger anti-diabetic drugs or insulin did not do so well. This could be a confounding bias because the milder patients with diabetes or milder symptoms of COVID-19 could have been put on Metformin whereas those who were sick could have been put on insulin. This could be a reverse causality – not because of the drug being useful but more severe cases using a different drug. Hence these factors are taken into account when a randomised clinical trial is conducted. From the same pool of people, one is randomising into two groups and in that sense, these are interesting results and strengthen the use of Metformin. Different studies are reinforcing that Metformin is the safest drug that has stood the test of time and I am happy to see the result,” he says.

Long Covid definition is evolving, more research needed

Dr Sanjay Pujari, infectious diseases expert and member of the Indian Council of Medical Research (ICMR) national COVID-19 task force, says the study has an interesting signal for use of Metformin in patients who have an acute COVID-19 episode and are at high risk of progressing to severe Covid (eventually towards a reduction in Long Covid symptoms). “However, results of the trial will not be applicable to everyone with acute COVID 19 because the definition of long Covid has been evolving throughout the pandemic, and basing efficacy analysis of the drug for preventing it can be tricky. Hence the translational benefit in public health needs more evidence,” Dr Pujari says. “Long Covid is a heterogeneous condition that cannot be defined easily. It involves multiple organs, persistence or occurrence of a new symptom or organ specific condition. There are generalized symptoms like fatigue, joint pain, brain fog, cardiac conditions and increasing incidence of blood sugar abnormalities and multiple studies have shown that 10-30 per cent may have Long Covid. There is not enough data,” he adds.

The first multi-centre randomised control trial

COVID-OUT is a first published randomised control trial (across six sites in the US) to suggest medication taken during the acute phase of COVID-19 may be able to reduce the risk of long COVID. Participants in the trial were not hospitalised, were at a higher risk of severe COVID-19 (overweight or obesity), over the age of 30, and had tested positive for SARS-CoV-2 within the last three days but had no known previous SARS-CoV-2 infection. Trial recruitment was open from December 2020 to January 2022 with 1,126 patients given either Metformin or an identical placebo pill after testing positive for SARS-CoV-2 during that time. Participants were followed up for 10 months with data gathered by self-report questionnaires every 30 days, according to the study funded by Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and the UnitedHealth Group Foundation.