Neither Metformin nor Ursodeoxycholic Acid Effectively Treats Postacute Sequelae of COVID-19 : A Randomized Clinical...

There is no proven treatment to alleviate symptoms of postacute sequelae of SARS-CoV-2 infection (PASC), despite its substantial public health burden.

To evaluate the efficacy of metformin and ursodeoxycholic acid (UDCA) in improving PASC symptoms in adults.

Double-blind, placebo-controlled, randomized clinical trial. (Clinical Research Information Service: KCT0009342).

Two tertiary hospitals in South Korea, July 2024 to April 2025.

Of 666 adults screened, 396 with a PASC index score of 12 or greater were randomly assigned.

Oral metformin (uptitrated to 1500 mg/d), UDCA (900 mg once daily), or double placebo for 14 days (1:1:1).

Proportion of participants achieving PASC recovery (index score <12) at 8 weeks.

Among 396 randomized participants (median age, 36 years [IQR, 28 to 49 years]; 72% women), 132 received metformin, 132 received UDCA, and 132 received placebo. The mean interval from SARS-CoV-2 infection was 9.8 months (SD, 7.5). The mean baseline PASC score was 19.3 (SD, 5.7). Recovery occurred in 63.6% (84 of 132) with metformin, 68.2% (90 of 132) with UDCA, and 68.2% (90 of 132) with placebo. Mean changes in PASC scores from baseline to week 8 were -10.05 (95% CI, -11.35 to -8.76) with metformin and -10.62 (CI, -11.79 to -9.45) with UDCA, compared with -10.43 (CI, -11.69 to -9.18) with placebo.

Findings may not be generalizable to patients with more severe or persistent long COVID.

A 2-week course of metformin or UDCA did not significantly improve recovery from PASC.

National Institute of Infectious Diseases, National Institute of Health, South Korea.