Cutting edge: Can diabetes medicine metformin improve Covid-19 outcomes?

The odds of emergency department visits, hospitalisations, and deaths went down by 40 to 50 per cent when prescribed early with the onset of symptoms – in those who were given the commonly prescribed diabetes medicine.

“Although we know Covid-19 vaccines are highly effective, we know that some new strains of the virus may evade immunity and vaccines may not be available worldwide. Understanding whether outpatient treatment could ensure more people survive the illness if they contract it and have fewer long-term symptoms is an important piece of the pandemic response,” said Carolyn Bramante, principal investigator of the study and an assistant professor of internal medicine and paediatrics at the University of Minnesota Medical School, in a release.

The clinical trial was launched in January 2021 after the researchers identified, through computer modelling and observational studies, that outpatient Metformin use appeared to decrease the likelihood of mortality and hospitalisation for Covid-19.

Several studies have reported favourable outcomes in Covid-19 patients who were on Metformin, including another analysis from the US published earlier this year that showed 0.83 per cent of people died of Covid-19 in the group that was on Metformin as compared to 4.02 per cent in the group that wasn’t.

Experts, however, say that such impacts could be a result of the underlying diabetes being well-controlled.

“There is no clear data to suggest that Metformin by itself results in better outcome for Covid-19 patients. However, there is sufficient data to show that good glucose control – an HbA1c (average blood glucose level over the past three months) of less than seven per cent — results in less severe disease and fewer complications. At least, that is what we saw when infections were caused by the first wave and the Delta variant,” said Dr Shashank Joshi, chair of the International Diabetes Federation-Southeast Asia and member of Maharashtra’s Covid-19 task force.

He added that the impact of diabetes and hypertension control was not as pronounced in disease caused by any of the Omicron sub-variants as it results in only upper respiratory tract infection in most people. “However, it is always a good idea to keep diabetes and hypertension under control,” he said.

However, the NEJM study, which was one of the few gold standard randomised control trials that looked at the impact of Metformin (along with an antidepressant Fluvoxamine and the anti-parasitic drug Ivermectin), did not achieve its primary outcome of reducing hypoxia.

The study included 1,323 participants who were overweight, with the patients being randomly assigned to receive one of the three drugs individually, placebo, or a combination of Metformin and Fluvoxamine or Metformin and Ivermectin. The participants received treatment for three to 14 days and tracked their symptoms. After 14 days, they completed a survey.

However, with the medicine already in wide use and no significant side-effects, experts say there is no harm in continuing it for those already using it. “It is very difficult to determine whether there was a better outcome in patients with one particular drug because they are usually on multiple medicines. However, other than controlling glucose levels, Metformin also has some anti-inflammatory properties. And, many studies have shown some benefits,” said Dr Anoop Misra, Executive Chairman and Director, diabetes and endocrinology, Fortis C-DOC Hospital.

He added, “Of course, being a randomised control trial, the NEJM study has more weightage and it did not meet the primary endpoint. But it is a medicine that is widely prescribed for diabetes, does not have much side effects other than some gastrointestinal issues, and can be continued for most even when they get Covid-19.”

So, can anyone pop the inexpensive medicine when they test positive for Covid-19? “No. It should only be continued in patients with diabetes or polycystic ovarian syndrome, who are already taking it,” said Dr Misra. Although the medicine can be continued in most Covid-19 patients, doctors may decide to replace it with injectable insulin in patients who have severe disease with unstable features, Dr Misra added.

“For patients with severe disease who need say oxygen support, Metformin may be discontinued because one, they cannot take the pill orally and two, it is not the best medicine for say people whose blood pressure or oxygen levels have dropped because it can result in lactic acidosis (build-up of lactic acid in the blood),” said Dr Misra.