Long COVID affects millions of people after SARS-CoV-2 infection (commonly known as COVID-19 infection). It can cause fatigue, brain fog, shortness of breath, and other lasting symptoms. Researchers report that metformin, a common diabetes drug, may help prevent Long COVID.
Metformin is a low-cost medication used worldwide to treat type 2 diabetes. Scientists have studied it for decades, and doctors understand its safety well. Evidence shows metformin may also protect people during acute COVID-19.
Why researchers studied metformin
Using a diabetes drug for a viral infection may sound surprising. However, scientists originally studied early forms of metformin for infectious diseases. Metformin also affects inflammation and immune responses in the body.
Early laboratory studies suggested metformin could interfere with SARS-CoV-2 replication. Observational studies during the pandemic strengthened that idea. These findings led researchers to test metformin as a treatment for COVID-19 in randomized clinical trials.
Long COVID treatment evidence from randomized trials
Two large trials, COVID-OUT and ACTIV-6, tested metformin in patients with acute COVID-19 infection. Both trials compared metformin with a placebo. Participants took the drug for 14 days shortly after infection.
Metformin and acute COVID-19 treatment
In the COVID-OUT trial, metformin reduced emergency room visits, hospitalization, or death from COVID-19 by 42%. When taken immediately after symptoms, metformin reduced serious outcomes by over 50%. Metformin reduced the COVID-19 viral load by 93.2 percent, compared with a 78.3 percent reduction with a placebo. Metformin also shortened the time to undetectable viral levels, averaging 3.3 days versus 5.6 days with placebo. And metformin reduced COVID-19 viral load by approximately 3.5-fold compared with placebo.
Metformin and Long COVID prevention
In the COVID-OUT trial, metformin reduced the risk of Long COVID by 41% overall. People who started metformin within three days saw even greater benefit. In that group, metformin reduced the risk of Long COVID by 63%. The Parsemus Foundation supported enrollment in several clinical trials of COVID-19 drugs, including the COVID-OUT study, and has previously shared those results.
The ACTIV-6 trial results, published in January 2026 in Clinical Infectious Diseases, confirmed the findings of the COVID-OUT trial in a broader population. This large, randomized, placebo-controlled study tested whether metformin could prevent Long COVID when started during acute COVID-19 infection. Unlike earlier trials, ACTIV-6 included adults with normal body weight and those with prior COVID-19 infection, broadening the study population.
Participants in the ACTIV-6 trial received metformin for 14 days, following the same dosing schedule as in the COVID-OUT trial. At six months, people who took metformin were about 50 percent less likely to report clinician-diagnosed Long COVID than those who received a placebo.
Across four high-quality studies, researchers have prevented one case of Long COVID for every 50 people treated. That finding shows a meaningful population-level impact.
Safety and access
Metformin showed a strong safety profile in all trials. Most participants tolerated it well, and serious side effects did not increase. The drug did not cause low blood sugar in people without diabetes.
Metformin’s common side effects include diarrhea, nausea, gas, bloating, abdominal pain, and indigestion, affecting up to 20% of users, especially at the start of treatment, but often improving over time or with extended-release (ER) versions. Other effects can include a metallic taste, headache, fatigue, and vitamin B12 deficiency with long-term use.
Doctors can also combine metformin with other COVID-19 treatments; there are no major drug interactions.
Most adults can take metformin, but they should talk with a clinician first. Researchers have not tested metformin in children for this purpose. And metformin does not treat existing Long COVID.
What this means now
Multiple trials now show metformin can prevent Long COVID when started soon after infection with COVID-19. The evidence applies to low-, standard-, and high-risk adults. It also applies in the current phase of the pandemic.
“This body of evidence means that starting metformin at the time of infection can reduce the risk of Long COVID for most adults who get COVID-19 today.”
— Carolyn Bramante, MD, MPH, assistant professor at the University of Minnesota Medical School and physician with M Health Fairview, and a lead investigator for the COVID-OUT and ACTIV-6 studies
Experts say that metformin warrants consideration in outpatient COVID-19 care. Adding it to guidelines could help prevent Long COVID at scale. For many adults, this simple approach could reduce long-term harm from COVID-19.
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