PLoS ONE (Jan 2022)

Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study.

  • Carolyn T Bramante,
  • Steven G Johnson,
  • Victor Garcia,
  • Michael D Evans,
  • Jeremy Harper,
  • Kenneth J Wilkins,
  • Jared D Huling,
  • Hemalkumar Mehta,
  • Caleb Alexander,
  • Jena Tronieri,
  • Stephenie Hong,
  • Anna Kahkoska,
  • Joy Alamgir,
  • Farrukh Koraishy,
  • Katrina Hartman,
  • Kaifeng Yang,
  • Trine Abrahamsen,
  • Til Stürmer,
  • John B Buse,
  • N3C core authors

DOI
https://doi.org/10.1371/journal.pone.0271574
Journal volume & issue
Vol. 17, no. 11
p. e0271574

Abstract

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BackgroundWhile vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size.MethodsConducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome.Results6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28-0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33-0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control.ConclusionsThere were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.