A new paper was published on March 31st 2026, titled ‘The Effect of Fluvoxamine and Metformin for Fatigue in Patients With Long COVID: An Adaptive Randomized Trial.' Dr Charles Shepherd, MEA Hon. Medical Adviser, provides comment on this research below.
Extracts:
Objective:
To assess the efficacy of fluvoxamine and metformin for long COVID fatigue.
Participants:
399 adults with fatigue persisting 90 or more days after confirmed SARS-CoV-2 infection.
Intervention:
Participants were randomly assigned to fluvoxamine (100 mg twice daily), metformin (750 mg twice daily), or matching placebo for 60 days.
Measurements:
The primary outcome was change in Fatigue Severity Scale (FSS) score.
Results:
Fluvoxamine showed a significant reduction in fatigue compared with placebo at day 60 (mean difference, −0.43 [95% credible interval {CrI}, −0.80 to −0.07]), with a sustained effect at day 90 (mean difference, −0.58 [CrI, −0.98 to −0.16]). Fluvoxamine also improved quality-of-life scores with high posterior probability. Metformin showed no significant benefit. Adverse events were less frequent with fluvoxamine (20.0%) than with metformin (28.8%) or placebo (29.7%). Grade 3 and higher adverse events were rare across all groups.
Limitations:
The 90-day follow-up period limits conclusions about the durability of treatment effects, and the exclusive focus on fatigue as the primary outcome does not address other prevalent long COVID symptoms, leaving fluvoxamine's broader therapeutic utility uncertain.
Conclusion:
Fluvoxamine, but not metformin, may be an effective treatment for reducing fatigue and improving quality of life in patients with long COVID.
MEA Comment:
We have recently been reporting on several clinical trials that are, or have been, taking place to assess whether metformin can be used to prevent and/or treat Long Covid.
Metformin is a drug that is normally used to reduce blood sugar in people who have type 2 diabetes. But is also has anti-inflammatory and immunomodulatory effects – which is why it might be an effective form of treatment for both Long Covid and ME/CFS.
However, the results so far are not very convincing and the results from this clinical trial add further doubt as to whether this drug can be used to prevent or treat Long Covid.
Fluvoxamine is an SSRI (selective serotonin reuptake inhibitor) drug that increases the level of a brain chemical transmitter called serotonin. It is normally use to treat psychiatric disorders – obsessive-compulsive disorder in particular.
Whilst the results from this trial suggest that fluvoxamine can reduce fatigue levels in people with Long Covid the results need to be viewed with caution, especially in relation to the way in which improvement over time does occur in a significant proportion of people with Long Covid.
It's also important to note that people with ME/CFS are often very sensitive to drugs like this which increase the level of serotonin in the brain and that a clinical trial involving a similar drug (fluoxetine/Prozac) in people with ME/CFS failed to have any effect on fatigue levels.
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
More Information:
- Metformin Survey (CLOSED) | September 18, 2025
- Metformin Survey Results | November 20, 2025