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Metformin and Time to Sustained Recovery in Adults With COVID-19: The ACTIV-6 Randomized Clinical Trial
Carolyn T Bramante1, Thomas G Stewart2, David R Boulware1
1Department of Medicine, University of Minnesota Medical School, Minneapolis.
JAMA Internal Medicine
|July 14, 2025
Summary
Metformin did not significantly shorten symptom duration for outpatient adults with COVID-19. This study found no significant difference in recovery time between metformin and placebo groups for SARS-CoV-2 infection.
Area of Science:
- Infectious Diseases
- Pharmacology
Background:
- The impact of metformin on COVID-19 symptom duration in outpatients was previously unstudied.
- Repurposed medications are being evaluated for treating mild to moderate COVID-19.
Purpose of the Study:
- To assess the efficacy of metformin compared to placebo in resolving symptoms during acute SARS-CoV-2 infection.
Main Methods:
- A randomized, placebo-controlled trial (NCT04885530) involving 2991 adults with COVID-19 symptoms for 7 days or less.
- Participants received daily metformin (titrated to 1500 mg) or placebo for 14 days.
- The primary outcome was time to sustained recovery, defined as 3 consecutive symptom-free days within 28 days.
Main Results:
- No significant difference was observed in the time to sustained recovery between the metformin and placebo groups (adjusted hazard ratio, 0.96; P=.11).
- Median time to sustained recovery was 9 days for metformin and 10 days for placebo.
- No deaths were reported; serious adverse events and hospitalizations were similar between groups, with minimal hypoglycemia episodes.
Conclusions:
- Metformin did not demonstrate a significant benefit in shortening symptom resolution time for low-risk adults with COVID-19.
- The drug was found to be safe, with no limitations observed in the study population.
- Further research may explore metformin in different patient populations or for other COVID-19 outcomes.
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