Metformin did not significantly reduce COVID-19 symptom duration in low-risk outpatients, according to a new study. The median recovery time was 9 days versus 10 days for placebo.

In a randomized clinical trial, researchers investigated whether metformin could shorten the duration of symptoms among outpatient adults with mild to moderate COVID-19. In addition to its use as a first-line treatment for type 2 diabetes, "metformin has also been shown to exhibit in vitro antiviral actions in studies with dengue, hepatitis C, and rotavirus," Carolyn T. Bramante, MD, MPH, of the Department of Medicine at the University of Minnesota Medical School, wrote with colleagues.

They added, "Observational and prospective analyses have reported that prevalent metformin use was associated with less severe outcomes during acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the COVID-OUT randomized trial of metformin vs placebo, hospitalization or death occurred for 1.3% of the metformin group and 3.2% of the placebo group, suggesting that further study was warranted to validate these findings." 

The trial enrolled 2,991 participants aged 30 years or older across 90 US sites between September 2023 and May 2024 during the predominance of the JN-1 SARS-CoV-2 subvariant.

Eligible participants had a confirmed SARS-CoV-2 infection and reported at least two COVID-19 symptoms for 7 days or less. Participants were randomly assigned in a 1:1 ratio to receive either immediate-release metformin or placebo. They self-administered oral metformin at a dose of 500 mg per day (one 500-mg tablet) for 1 day, followed by 500 mg twice a day for 4 days, followed by 500 mg in the morning and 1000 mg in the evening for 9 days, for a 14-day course of 36 total tablets. The primary endpoint was time to sustained recovery, defined as 3 consecutive days without symptoms within 28 days of receiving the study drug. Secondary endpoints included health care utilization and safety events.

Of the modified intention-to-treat population, 1,443 participants received metformin and 1,548 received placebo. The median age was 47 years (interquartile range = 38–58), and 63.4% were female. COVID-19 vaccination with two or more doses was reported by 68.3% of participants. The median time to sustained recovery was 9 days (95% confidence interval [CI] = 9–10) in the metformin group and 10 days (95% CI = 9–10) in the placebo group. The adjusted hazard ratio (aHR) was 0.96 (95% credible interval [CrI] = 0.89–1.03) with a posterior probability of benefit of 0.11, which indicated no significant difference between groups.

Regarding secondary outcomes, 3.7% of metformin recipients and 3.2% of those who received placebo reported a clinic visit, emergency department visit, hospitalization, or death by day 28 (aHR = 1.25, 95% CrI = 0.82–1.78). No deaths occurred. The incidence of emergency department visits or hospitalization was 1% in the metformin group and 1.3% in the placebo group. Serious adverse events were rare (0.36% overall), and there were no cases of lactic acidosis. Hypoglycemia was reported in 0.14% of participants who received metformin and 0.26% of those who received placebo.

Full disclosures can be found in the published study.

Source: JAMA Internal Medicine