A new study suggests that metformin, the world’s most-prescribed diabetes drug, significantly reduces the incidence of long COVID. Trial volunteers with a positive COVID-19 diagnosis who were randomly assigned to take metformin for two weeks were nearly half as likely to later be diagnosed with long COVID.
The study has been published online as a pre-print by The Lancet.
Conducted at multiple sites in the United States, the experiment enrolled overweight and obese adults (ages 30 to 85) with active cases of COVID-19. Some were randomly assigned to receive two weeks of metformin, others a placebo.
Three hundred days later, the researchers evaluated how many of the volunteers had been diagnosed with long COVID. The results:
10.6 percent of participants who received a placebo were diagnosed with long COVID
6.3 percent of participants who received metformin were diagnosed with long COVID
Metformin’s benefit was consistent across all subgroups
The bottom line: a “42 percent relative decrease and 4.3 percent absolute decrease” in the incidence of long COVID.
It’s not yet clear exactly why metformin might have this beneficial effect, though the drug is known to reduce inflammation and suppress the novel coronavirus’ ability to replicate.
The same trial also evaluated the effect of fluvoxamine, an antidepressant, and ivermectin, an antiparastic drug controversially promoted on social media. Both fluvoxamine and ivermectin were ultimately rejected by the medical establishment as COVID-19 therapies. Neither medication had a significant effect on long COVID incidence.
Long COVID
Long COVID remains something of a mystery. The condition consists of a very wide range of symptoms, many of them difficult to assess objectively. The mechanisms by which COVID-19 causes long COVID are still unknown. And while various treatments can help manage the symptoms, experts have yet to identify any drug or therapy to address the root cause.
The Centers for Disease Control and Prevention (CDC) offer a non-comprehensive list of 19 diverse symptoms of long COVID, including fever, diarrhea, mood changes, and “brain fog.” These symptoms can last weeks, months, or years, and can disappear only to return again.
A recent review in Nature Reviews Microbiology states that long COVID occurs in “at least 10 percent” of severe SARS-CoV-2 infections. Tens of millions of people are affected worldwide. In the most serious cases, such as when long COVID causes chronic fatigue syndrome or dysautonomia, the disease can be debilitating.
Long COVID also has an unfortunate association with diabetes. Experts believe that people with diabetes are far more likely to experience the symptoms of long COVID and that long COVID is associated with worsening glycemic management.
Today, prevention is the only way to reduce long COVID’s public health impact. Avoiding infection in the first place, of course, is the best way to prevent long COVID, and there is evidence that the COVID-19 vaccines may help, too. But until now, there has been no way for people already infected with COVID-19 to reduce their risk of long COVID. Metformin may become the first option.
Will Doctors Begin Prescribing Metformin for long COVID Prevention?
Metformin is inexpensive and widely available. Although it gives some users unpleasant side effects, it is considered a safe and predictable drug. Is this single trial strong enough evidence for doctors to begin prescribing metformin to people with COVID-19?
Eric Topol, MD, says “yes.” Dr. Topol is a cardiologist and professor at the Scripps Research Institute; he discussed the new study in the latest edition of his Substack newsletter:
… to see such a pronounced benefit in the current randomized trial of metformin, in the context of it being so safe and low cost, I’d give it a breakthrough categorization. Another way to put it, that unless or until there are data to the contrary, if I got COVID, I’d take metformin for 2 weeks at the doses used in this trial.
Topol’s recommendation is striking given his history — he made national news in 2020 when he forcefully advocated for the Food and Drug Administration (FDA) not to rush its approval of the first COVID-19 vaccines. In the same letter, he criticized the FDA’s prior decision to grant an Emergency Use Authorization for hydroxychloroquine, a potential COVID-19 remedy touted by President Donald Trump that was largely untested at the time. To put it simply, Topol has a very public history of arguing for caution in the novel use of drugs.
Metformin is automatically prescribed to most people with type 2 diabetes in the United States. It is also popular as an off-label adjunct therapy in type 1 diabetes, though users should be mindful that the drug can significantly affect insulin requirements.
A single study, even a randomized controlled trial, is not typically considered enough to drive public health policy changes, and some clinicians will undoubtedly want to wait for further studies to confirm metformin’s positive effect before they feel comfortable prescribing it to patients with COVID-19. Some, however, may follow Topol’s example, and be eager to prescribe metformin to their patients in the hopes that it might prevent the development of long COVID.