Metformin and ursodeoxycholic acid both fail to improve long COVID recovery in new clinical trial

A randomized clinical trial found that a two-week course of metformin or ursodeoxycholic acid (UDCA) did not meaningfully improve recovery from long COVID symptoms, despite earlier evidence suggesting metformin could lower long-term risk when taken during acute infection. The findings underscore the continued lack of proven treatments to alleviate symptoms of long COVID. The study is published in Annals of Internal Medicine.

Researchers from Asan Medical Center and Hallym University Kangnam Sacred Heart Hospital in Seoul tested whether short-term treatment with metformin, a common diabetes drug shown to reduce the incidence of long COVID by 41%, or UDCA, a liver medication with potential antiviral and immunomodulatory effects, could ease long COVID symptoms months after infection.

Researchers randomly assigned 396 adults with persistent symptoms to receive metformin, UDCA, or placebo for two weeks in a double-blind trial conducted at two hospitals in South Korea between July 2024 to January 2025, with follow-up completed in April 2025. After eight weeks, recovery rates and symptom improvements were similar across all three groups, indicating neither drug helped patients recover faster or more completely than placebo.

The authors conclude that while long COVID remains a major public health challenge, these widely used medications do not appear to offer a solution when given after symptoms have already developed.

The findings highlight the need for further studies to support the development of targeted therapies addressing immune dysregulation in long COVID pathophysiology.

Reference:

So Yun Lim, Jacob Lee, Euijin Chang, et al. Neither Metformin nor Ursodeoxycholic Acid Effectively Treats Postacute Sequelae of COVID-19: A Randomized Clinical Trial. Ann Intern Med. [Epub 3 March 2026]. doi:10.7326/ANNALS-25-04883