A new observational study examined whether metformin prescribed within the first week of SARS-CoV-2 infection reduces the risk of Long COVID - what it actually shows🧵
The authors used N3C electronic health records and a target trial emulation design to compare metformin vs several other COVID-related prescriptions.
After weighting, both groups had ~248 people.
The outcome was Long COVID (ICD-10 U09.9 or a computable phenotype) or death within 180 days.
The outcome was Long COVID (ICD-10 U09.9 or a computable phenotype) or death within 180 days.
Results.
Metformin group 4.0%
Control group 8.5%
Adjusted risk ratio 0.47
This suggests roughly a 50% lower risk of Long COVID/death when metformin is prescribed early.
The effect appeared stronger when treatment was given on day 0-1.
Metformin group 4.0%
Control group 8.5%
Adjusted risk ratio 0.47
This suggests roughly a 50% lower risk of Long COVID/death when metformin is prescribed early.
The effect appeared stronger when treatment was given on day 0-1.
This is consistent with earlier signals.
The COVID-OUT randomized trial (also showing reduced LC risk)
Trials showing lower viral loads with metformin
Mechanistic work pointing to antiviral and immunomodulatory effects.
So yes - the overall direction is consistent.
The COVID-OUT randomized trial (also showing reduced LC risk)
Trials showing lower viral loads with metformin
Mechanistic work pointing to antiviral and immunomodulatory effects.
So yes - the overall direction is consistent.
But it’s still important to keep perspective.
This is another observational study!
Long COVID identification in EHRs is imperfect, actual medication use is unknown, and the effective sample size is small.
This is another observational study!
Long COVID identification in EHRs is imperfect, actual medication use is unknown, and the effective sample size is small.
And the study was led by the same team that ran the original metformin RCT - which means this is not independent replication, but an internal consistency check.
Useful, but not a replacement for external confirmation.
Useful, but not a replacement for external confirmation.
Still, for many people with no accessible early treatments, every positive signal matters.
Metformin continues to be one of the very few interventions repeatedly showing potential benefit.
Metformin continues to be one of the very few interventions repeatedly showing potential benefit.
But we need independent, larger, rigorously designed studies - not more analyses coming from the same research circle.
We need a completely different level of effort. Truly independent teams, publicly funded programs, preregistered protocols, long-term follow-up, and transparent methods.
We need studies defining Long COVID with biological markers, not billing codes.
And above all, studies that provide independent, reproducible evidence that patients and clinicians can trust.
Long COVID is far too serious for partial evidence. People deserve better - and so does the science.
And above all, studies that provide independent, reproducible evidence that patients and clinicians can trust.
Long COVID is far too serious for partial evidence. People deserve better - and so does the science.
Bramante at al., Metformin at the time of Covid-19 infection and risk of Long Covid: A Target Trial Emulation Study. authorea.com/users/1004233/…
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