03 Apr UBC Scientists Find a Drug that Works for Long COVID Fatigue

MedicalResearch.com Interview with:
Jamie I Forrest PhD, MPH
Scientific Director, Health Equity & Resilience Observatory (HERO)
Faculty of Applied Science
University of British Columbia

MedicalResearch.com: What is the background for this study?

Response: We’ve known since early in the pandemic that many people don’t fully recover after COVID-19. Fatigue is one of the most persistent and disabling symptoms, and it significantly reduces quality of life — affecting people’s ability to work, care for their families, and participate in daily life.

Until now, there have been very few treatment options backed by solid evidence. Doctors have largely focused on supportive care — helping patients manage their symptoms through rest, pacing, and multidisciplinary teams — because no medication had been shown to work in a well-designed clinical trial. Several smaller or uncontrolled studies had suggested certain drugs might help, but robust randomized controlled trial evidence was scarce.

Interestingly, metformin had previously been shown to reduce the risk of developing Long COVID when taken during the acute phase of infection. Our study asked a different question: can these drugs help people who already have established Long COVID?

Long COVID — also called post-acute sequelae of SARS-CoV-2, or PASC — is a condition where people continue to feel sick for months or even years after recovering from a COVID-19 infection. The most common and debilitating complaint is fatigue: a profound, persistent exhaustion that doesn’t get better with rest and can make even simple daily activities feel impossible. Despite affecting an estimated tens of millions of people worldwide, there are almost no proven treatments.

We wanted to test whether two existing, widely available, and affordable medications could help. The first was fluvoxamine — an antidepressant that also has potent anti-inflammatory effects and acts on brain pathways involved in fatigue. The second was metformin — a common diabetes medication that reduces inflammation and may support cellular energy production. Both had biological reasons to think they might work against Long COVID fatigue, but neither had been rigorously tested for this purpose in a proper clinical trial.

MedicalResearch.com: What are the main findings?

Response:  Fluvoxamine worked. Patients taking fluvoxamine had significantly lower fatigue scores compared to those taking a placebo after 60 days, and this improvement was sustained even 30 days after they stopped the medication (at Day 90). They also reported meaningful improvements in their overall quality of life. The statistical probability that fluvoxamine was genuinely better than placebo was 99% — an exceptionally strong result.

Metformin did not work. There was no meaningful difference in fatigue between patients taking metformin and those on placebo. The trial’s independent safety monitoring board stopped the metformin arm early because the data clearly showed it was not going to be effective.

Both treatments were safe. Serious adverse events were rare and occurred at similar rates across all groups. There were no treatment-related deaths.

What makes this novel: This is one of the first rigorous, randomized, placebo-controlled clinical trials to identify a medication that meaningfully reduces fatigue in people with established Long COVID. The trial used a sophisticated “adaptive” design that allowed it to reach conclusions more efficiently than traditional trials, stopping early when the evidence was clear enough — a design innovation as important as the findings themselves. 

MedicalResearch.com: Who do you think is the audience for this research? Why should it matter to them? 

Response: This research has a very broad and urgent audience. The most directly affected are the estimated 65+ million people worldwide living with Long COVID — many of whom have had little hope of effective pharmacological treatment. Patient advocacy organizations (such as Long COVID Alliance, Survivor Corps, and similar groups in Canada and Brazil) will likely want to share these findings widely.

Clinicians — particularly family physicians, internists, and infectious disease specialists — are hungry for evidence-based treatment options to offer patients. This gives them a concrete, actionable finding.

Public health agencies and health systems are grappling with the long-term burden of Long COVID on the workforce and healthcare systems. Policymakers in Canada, Brazil, and globally will find this directly relevant to Long COVID care guidelines.

The scientific and clinical research community will also be interested in the adaptive Bayesian trial design used, which can serve as a model for future therapeutic trials in Long COVID and post-viral syndromes more broadly.

Disclosures?
Response: The Latona Foundation. The Latona Foundation had no role in study design, data collection, data analysis, data interpretation, or writing of the report and the authors report no conflicts of interest.

Citation:

Gilmar Reis, Eduardo Augusto dos Santos Moreira Silva, Daniela Carla Medeiros Silva, et al. The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID: An Adaptive Randomized Trial. Ann Intern Med. [Epub 31 March 2026]. doi:10.7326/ANNALS-25-03959

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Last Updated on April 3, 2026 by Marie Benz MD FAAD