Metformin after COVID: What the new long-COVID trial found

If you test positive for COVID-19, this new study does not mean most people should start metformin on their own. In the June 4, 2026 ACTIV-6 randomized trial, metformin did not meet its main goal of lowering participant-reported post-COVID symptoms at 180 days. A secondary analysis found fewer clinician-diagnosed long-COVID cases in the metformin group, but that finding is not enough to make metformin a routine prevention strategy.

What ACTIV-6 studied

ACTIV-6 was a randomized, placebo-controlled trial in 2,983 outpatients age 30 and older with confirmed SARS-CoV-2 infection and at least two symptoms. People were enrolled within 7 days of symptom onset at 90 sites between September 19, 2023, and May 1, 2024, and they took metformin or placebo for 14 days. The main outcome was whether participants still reported symptoms they attributed to COVID-19 on day 180. Clinician-diagnosed long COVID was a secondary outcome.

What the trial found

By day 180, the adjusted difference in participant-reported symptoms was small, and the study did not meet its prespecified threshold for success on the primary endpoint. In plain language, the trial did not show a clear win for metformin on its main test.

The secondary result looked more encouraging: clinician-diagnosed long COVID was lower in the metformin group. But because that was a secondary outcome, and the main endpoint was not met, this should be treated as a signal worth studying further, not as proof that metformin should be used routinely to prevent long COVID.

Why the result is mixed

The study population matters. These were outpatients, many had some prior immunity from past infection or vaccination, and there were no deaths in the trial. That helps explain why the absolute differences were small and why the findings may not apply the same way to higher-risk patients or other groups.

The main outcome also depended on self-reported symptoms. Long COVID is real and can be disabling, but CDC says there is still no approved laboratory test to confirm it and no approved treatment specifically for it.

What current guidance still says

CDC says anyone who gets COVID-19 can develop long COVID, and that vaccination remains an important prevention step. For people at higher risk of severe illness, CDC and IDSA continue to emphasize prompt evaluation for standard antiviral treatment rather than waiting to see whether an off-label option might help later.

For acute COVID-19, timing matters. CDC says treatment should start as soon as possible, with oral nirmatrelvir-ritonavir within 5 days of symptom onset and outpatient remdesivir within 7 days for eligible patients.

Should you ask about metformin?

It may be reasonable to bring up the study with a clinician, but metformin is not something to start casually because of a headline. It is widely used for type 2 diabetes, and MedlinePlus warns that it can rarely cause serious lactic acidosis and may not be safe for some people with kidney disease or other conditions. A clinician would need to consider kidney function, age, other illnesses, and medication interactions before prescribing it for any off-label use.

If you are older, immunocompromised, pregnant, or have another condition that raises the risk of severe COVID-19, the more urgent question is whether you qualify for standard treatment now while you are still in the treatment window.

What readers can do now

If you test positive and have risk factors for severe COVID-19, contact a clinician quickly to ask whether you qualify for standard antiviral treatment.
Do not start metformin on your own to try to prevent long COVID.
Stay up to date on COVID-19 vaccination.
If you develop emergency warning signs such as trouble breathing, persistent chest pain or pressure, or new confusion, seek emergency care.

What remains unknown

This trial does not answer whether metformin should be used routinely after every positive COVID test. Future studies would need to identify which patients, if any, benefit most; how soon treatment must start; how metformin compares with approved antivirals; and whether any benefit holds up across different ages and risk groups. For now, the new study adds an interesting but incomplete signal, not a new standard of care.

Sources

Editorial note: Weence articles are researched from cited public-health, medical, regulatory, journal, and reputable news sources and may be drafted with AI assistance. They are checked for source support, clarity, and safety guardrails before publication.

This article is for general informational purposes only and is not medical advice. Research findings can be early or incomplete, and health guidance can change. Always talk with a qualified healthcare professional about personal symptoms, diagnosis, medications, vaccines, screenings, or treatment decisions. If you think you may have a medical emergency, call emergency services right away.