This Common Diabetes Drug May Lower Long COVID Risk

According to a new study, a medication frequently prescribed to treat type 2 diabetes may reduce the risk of long COVID when taken during the acute phase of infection.

The medication, called metformin, was one of several medications researchers tested against long COVID in a phase 3 clinical trial called COVID-OUT.

While researchers also tested an antiparasitic drug called ivermectin and an antidepressant called fluvoxamine against placebos, only outpatient treatment with metformin decreased the risk of long COVID by 41.3%.

The timing of treatment mattered, though; starting the two-week course of metformin less than four days after the onset of COVID symptoms was more effective than starting treatment four or more days after COVID symptoms started. The study focused on curbing long COVID risk during the acute phase of a COVID infection.

The study included over 1,100 people with COVID who had:

• Overweight or obesity
• COVID symptoms for fewer than seven days
• No known previous SARS-CoV-2 infection

The study did not look at the effectiveness of metformin for preventing long COVID if the treatment was started while a patient was in the hospital. It also did not look at the effectiveness of the drug as a treatment for people who already had long COVID.

Why Metformin May Reduce Long COVID Risk

According to study author David Liebovitz, MD, an internal medicine specialist at Northwestern Medicine, the exact way that metformin works against long COVID is still unknown.

One hypothesis is that metformin could directly target the SARS-CoV-2 virus. The study showed that starting metformin treatment earlier was linked to a stronger preventive effect against long COVID—not unlike how an antiviral treatment would work. 

“Having a safe, inexpensive, and widely-available drug that significantly reduces the incidence of long COVID would greatly impact the large burden of illness conferred by new cases of long COVID,” Liebovitz told Verywell.

A preprint study (which has yet to be peer-reviewed) from the COVID-OUT trial found that metformin reduced participants’ mean SARS-CoV-2 viral load by more than threefold compared to placebo.

Other studies have suggested that the higher a person’s viral load is, the higher their risk for severe COVID symptoms and post-COVID symptoms. So using metformin to reduce the amount of virus in the body early on makes sense.

Liebovitz added that metformin is able to reduce oxidative stress on cells, as well as reduce inflammation. Previous research has identified the potential of repurposing metformin as a COVID treatment specifically for its antiviral and anti-inflammatory effects.

Researchers believe the drug may help quiet “cytokine storms,” the overproduction and uncontrolled release of pro-inflammatory cytokines that some researchers think could contribute to long COVID.

Will Metformin Be Used to Try to Prevent Long COVID?

Although this study adds to the evidence for the use of metformin in tandem with COVID, it is still not considered a recommend treatment by the Centers for Disease Control and Prevention (CDC).

“It is possible this may change, or additional confirmatory studies may need to be published prior to its inclusion,” Liebovitz said.

Metformin is commonly prescribed for people with diabetes, but it can also be used to treat some symptoms of polycystic ovary syndrome (PCOS) by improving insulin sensitivity and promoting ovulation.

If metformin becomes a COVID treatment drug, demand could increase and people who take it for these conditions could face shortages—though experts don’t think that’s a concern yet. Given the short course of metformin treatment as well as multiple manufacturers and formulations, Liebovitz said “a shortage would not appear likely for this widely available, safe, generic medication.”

Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security, told Verywell that a shortage would be unlikely, but added that it will be important to assess supply chain resiliency should demand for metformin increase.

Defining a Disease

The definition of long COVID evolved throughout the pandemic and healthcare providers and researchers still do not characterize the condition the same way.

Adalja said that not having a clear definition and diagnostic criteria “does hamper the development of treatments and preventatives” for long COVID, but that doing research while acknowledging the limitations is beneficial. That’s the only way to lead to new discoveries and a better understanding of the condition.

For the recent trial, the researchers used follow-up surveys to ask participants whether they had received a long COVID diagnosis on days 180, 210, 240, 270, and 300 after infection. This helped the researchers rule out other explanations for the patients’ lasting symptoms, which meets the World Health Organization’s definition of long COVID.

The authors believe that the long follow-up and the way they identified long COVID cases based on the professional judgment and diagnosis of the participants’ providers would have helped address concerns about the differences in defining the condition.

Although emerging or newly-characterized conditions may have changing criteria for research, Liebovitz said the burden of a condition like long COVID is clear.

“The impact on patients’ lives and livelihoods is tremendous,” he said.

Many Americans are living with long-term symptoms, limited physical mobility, and impaired cognitive function after having COVID. Given the lasting “legacy” that COVID leaves, Liebovitz said that “making headway against this new scourge is of paramount importance.”