Metformin reduces the risk of Long COVID or Death over 6 months in an Emulated Target Trial of Primarily Omicron-infected Adults without Diabetes or Prediabetes: a New-User, Active-Comparator Analysis Using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database. This research was supported in part by the Intramural/Extramural research program of the National Center for Advancing Translational Science, NIH

Abstract: PhD6; 1University of Minnesota, Minneapolis, MN; 2University of North Carolina, Chapel Hill, Chapel Hill, North Carolina; 3Duke University, Durham, North Carolina; 4 University of Virginia, Charlottesville, Virginia; 5National Institute of Health, Bethesda, Maryland; 6Scripps Research, San Diego, California Study Group: n/a Session: 253. Late Breaker Abstract Session: What’s Going Viral Saturday, October 19, 2024: 2:21 PM 3 /µL; P=0.23). Cumulative incidence curves for the outcome of Long Covid/Death in the 180 Days after a metformin prescription (blue) or active comparator prescription (red). The increase in outcomes at Day 90 reflects the computable phenotype, which cannot be computed until 90 days after infection. Per data use requirements in the National Covid Cohort Collaborative (N3C), the starting number at risk is not shown due to small cell sizes or the ability to calculate small cell sizes. Methods. We emulated a randomized trial of metformin vs. control in SARS-CoV-2-infected outpatients. Intervention: prescription for metformin within 6 days of infection. Control: prescription for fluvoxamine, fluticasone, ivermectin, or montelukast (drugs used off-label for Covid but clinical trials have shown no effect on acute COVID outcomes). Exclusions: age < 18; metformin or comparator prescribed within 365 days; indication for chronic metformin use; contraindication for metformin or control. Outcome: a composite of LC or Death (LC/D), LC defined by U09.9 or a symptom/condition based computable phenotype. We used entropy balancing to estimate the average treatment effect with a weighted log linear model. This is a forest plot showing metformin use versus active comparator use and the development of Long Covid/Death by Day 180. Abstract citation ID: ofae631.016 578. Metformin reduces the risk of Long COVID or Death over 6 months in an Emulated Target Trial of Primarily Omicron-infected Adults without Diabetes or Prediabetes: a New-User, Active-Comparator Analysis Using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database. This research was supported in part by the Intramural/Extramural research program of the National Center for Advancing Translational Science, NIH Carolyn Bramante, MD, MPH1; Til Sturmer, MD, PhD2; Jared Huling, PhD1; John Buse, MD, PhD2; Steve Johnson, PhD1; Christopher Lindsell, PhD3; Thomas Stewart, PhD4; David Sahner, MD5; Sarah Dunsmore, PhD5; Eric Topol, MD, S10 • OFID 2025:12 (Suppl 1) • Late Breaking Abstracts The black squares represent risk ratios (RR), and the lines represent 95% confidence intervals. The number of outcomes, denominators, and exact percentages are sometimes omitted so that cell sizes <10 are not able to be calculated, in accordance with the data use requirements in the National Covid Cohort Collaborative (N3C). The Pre-Omicron Era is larger than the Omicron era in both the Metformin and Comparator Cohorts, but the denominator for the Day 0-6 sample is not shown because of cell sizes <10. The subgroup of those with new Background. Metformin has decreased SARS-CoV-2 RNA in 4 cell lines. In a RCT of > 1,000 majority vaccinated outpatients, COVID-19 related ED visits/ Hospitalization/Death occurred in 4.7% of the metformin vs 9.0% of the placebo group by Day 28; clinician-diagnosed Long Covid (LC) occurred in 6.2% of metformin vs 10.3% of placebo by..