Metformin at the Time of COVID‐19 Infection and Risk of Long COVID: A Target Trial Emulation Study
11 affiliations
- 1Department of Medicine, Division of General Internal Medicine, University of MN Medical School, Minneapolis, Minnesota, USA.
- 2Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
- 3Division of Biostatistics and Health Data Science, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA.
- 4Department of Medicine, Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
- 5Division of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA.
- 6Division of Biostatistics, University of Virginia School of Data Science, Charlottesville, Virginia, USA.
- 7Vanderbilt Institute for Medicine and Public Health, Nashville, Tennessee, USA.
- 8National Center for Advancing Translational Science (NCATS), Bethesda, Maryland, USA.
- 9NCATS contractor Axle Informatics, Rockville, Maryland, USA.
- 10Scripps Research Translational Institute, La Jolla, California, USA.
- 11Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota, USA.
Abstract
Our objective was to evaluate metformin prescribed at the time of SARS-CoV-2 infection on the risk of developing Long COVID (LC) in electronic health record data. We conducted a new user analysis of metformin prescribed within 6 days of documented infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus experimental control: prescription for fluvoxamine, fluticasone, ivermectin, or montelukast.Inclusion criteria
a clinic visit in the 0-6 months and the 6-12 months before infection.Exclusion criteria
metformin or control within 12 months.Primary outcome
LC or death (LC/D), to address death as a competing risk, among patients prescribed drug within Days 0-6 of infection. LC was defined by diagnosis code or computable phenotype. We used entropy balancing to estimate the average treatment effect with a weighted log-linear model. After weighting, there were 248 in the metformin and control groups; the average age was 53 (16); 16% were Black; and 16% were Hispanic. In the primary analysis, 10/248 (4.0%) in the metformin group developed LC/D versus 21/248 (8.5%) in the control group, adjusted risk ratio (aRR) 0.47 (95% CI 0.25-0.89, p = 0.02). For prescriptions on Days 0-1 relative to infection, aRR was 0.39 (95% CI 0.12-1.24); for prescriptions on Days 0-14, the aRR was 0.75 (95% CI 0.52-1.08). In this observational analysis, metformin prescribed within a week of documented SARS-CoV-2 infection was associated with a 53% lower risk of LC over 6 months than comparator medications. With the aRR of 0.47 (95% CI 0.25-0.89), any risk reduction between 75% and 11% is highly compatible with our data. This analysis of electronic health record diagnoses is important for the reproducibility of clinical trial results that ascertained the same outcome but via participant-report.
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BibTeX
@article{bramante2026metformin,
title = {{Metformin at the Time of COVID‐19 Infection and Risk of Long COVID: A Target Trial Emulation Study}},
author = {Carolyn T Bramante and Til Stürmer and Jared D Huling and John B Buse and Christopher Lindsell and Thomas Stewart and Russell L Rothman and David Sahner and Sarah E Dunsmore and Eric Topol and Talia D Wiggen and Steve Makkar and Andrew Toler and Taylor Estepp and Steven G Johnson and N3C Consortium},
journal = {Journal of medical virology},
year = {2026},
month = oct,
doi = {10.1002/jmv.71190},
url = {https://europepmc.org/article/PMC/PMC13717933},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metformin at the Time of COVID‐19 Infection and Risk of Long COVID: A Target Trial Emulation Study
AU - Carolyn T Bramante
AU - Til Stürmer
AU - Jared D Huling
AU - John B Buse
AU - Christopher Lindsell
AU - Thomas Stewart
AU - Russell L Rothman
AU - David Sahner
AU - Sarah E Dunsmore
AU - Eric Topol
AU - Talia D Wiggen
AU - Steve Makkar
AU - Andrew Toler
AU - Taylor Estepp
AU - Steven G Johnson
AU - N3C Consortium
PY - 2026
DA - 2026/10/29
JO - Journal of medical virology
DO - 10.1002/jmv.71190
UR - https://europepmc.org/article/PMC/PMC13717933
AB - Our objective was to evaluate metformin prescribed at the time of SARS-CoV-2 infection on the risk of developing Long COVID (LC) in electronic health record data. We conducted a new user analysis of metformin prescribed within 6 days of documented infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) versus experimental control: prescription for fluvoxamine, fluticasone, ivermectin, or montelukast.Inclusion criteria a clinic visit in the 0-6 months and the 6-12 months before infection.Exclusion criteria metformin or control within 12 months.Primary outcome LC or death (LC/D), to address death as a competing risk, among patients prescribed drug within Days 0-6 of infection. LC was defined by diagnosis code or computable phenotype. We used entropy balancing to estimate the average treatment effect with a weighted log-linear model. After weighting, there were 248 in the metformin and control groups; the average age was 53 (16); 16% were Black; and 16% were Hispanic. In the primary analysis, 10/248 (4.0%) in the metformin group developed LC/D versus 21/248 (8.5%) in the control group, adjusted risk ratio (aRR) 0.47 (95% CI 0.25-0.89, p = 0.02). For prescriptions on Days 0-1 relative to infection, aRR was 0.39 (95% CI 0.12-1.24); for prescriptions on Days 0-14, the aRR was 0.75 (95% CI 0.52-1.08). In this observational analysis, metformin prescribed within a week of documented SARS-CoV-2 infection was associated with a 53% lower risk of LC over 6 months than comparator medications. With the aRR of 0.47 (95% CI 0.25-0.89), any risk reduction between 75% and 11% is highly compatible with our data. This analysis of electronic health record diagnoses is important for the reproducibility of clinical trial results that ascertained the same outcome but via participant-report.
SN - 0146-6615
SN - 1096-9071
ER -