Metformin fails to Significantly Accelerate resolution of COVID-19 Symptoms in Low-Risk Adults: JAMA

A new study published in the Journal of American Medical Association showed that metformin did not significantly reduce the time to symptom resolution in low-risk adults with COVID-19, despite a numerically shorter median recovery time. So far, the ability of metformin to shorten the duration of symptoms in COVID-19 outpatient adults has not been investigated. Thus, this study evaluated the effectiveness of metformin in terms of symptom remission after an acute SARS-CoV-2 infection.

The platform of Accelerating COVID-19 Therapeutic Interventions and Vaccines assessed repurposed drugs for mild to moderate COVID-19. The participants 30 years or older with proven SARS-CoV-2 infection and 2 or more COVID-19 symptoms for 7 days or fewer were recruited at 90 US locations between September 19, 2023, and May 1, 2024.

For 14 days, participants were randomly assigned to receive either a placebo or metformin (titrated to 1500 mg, daily). Time to sustained recovery (3 days in a row without COVID-19 symptoms) over 28 days of starting the study medication was the main outcome. Time to clinic appointment, ED visit, hospitalization, or death were examples of secondary outcomes.

The median age of the 2,991 randomized participants who received the study drug was 47 years (IQR, 38-58); 1895 (63.4%) were female, 25 (0.8%) were American Indian or Alaska Native, 350 (11.7%) were Black, African American, or African, 1,392 (46.5%) identified as Hispanic or Latino, 77 (2.6%) were Asian, 8 (0.3%) were Native Hawaiian or other Pacific Islander, 2395 (80.1%) were White, and 2044 (68.3%) reported receiving two or more doses of the SARS-CoV-2 vaccine.

There were no differences in the time to sustained recovery between the 1443 (48.2%) patients who got metformin and the 1548 (51.8%) who received a placebo (adjusted hazard ratio, 0.96; 95% credible interval [CrI], 0.89-1.03; P for effectiveness =.11). For metformin, the median duration to sustained recovery was 9 days (95% CI, 9–10), while for a placebo, it was 10 days (95% CI, 9–10).

There were no recorded fatalities, and 103 participants (54 in the metformin group and 49 in the placebo group) reported clinic visits, emergency department visits, or hospitalizations (hazard ratio, 1.25; 95% CrI, 0.82-1.78; P for effectiveness =.13). In all, 35 people (1.2%) experienced hospitalization or ED visits (1.1% in the metformin group and 1.3% in the placebo group). Over the course of 180 days, three people who received a placebo and seven who received metformin encountered a major adverse event.

The metformin group experienced 2 bouts of participant-reported hypoglycemia, whereas the placebo group experienced 4. Overall, metformin did not reduce the duration to symptom remission in low-risk persons with COVID-19, according to this randomized clinical study.

Reference:

Bramante, C. T., Stewart, T. G., Boulware, D. R., McCarthy, M. W., Gao, Y., Rothman, R. L., Mourad, A., Thicklin, F., Cohen, J. B., Garcia Del Sol, I. T., Ruiz-Unger, J., Shah, N. S., Mehta, M., Cardona, O. Q., Scott, J., Ginde, A. A., Castro, M., Jayaweera, D., Sulkowski, M., … Accelerating COVID-19 Therapeutic Interventions and Vaccines-6 Study Group and Investigators. (2025). Metformin and time to sustained recovery in adults with COVID-19: The ACTIV-6 randomized clinical trial: The ACTIV-6 randomized clinical trial. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2025.2570