Metformin is associated with reduced COVID-19 severity in patients with prediabetes

Lauren E. Chan, Elena Casiraghi, Bryan Laraway, Ben Coleman, Hannah Blau, Adnin Zaman, Nomi L. Harris, Kenneth Wilkins, Blessy Antony, Michael Gargano, Giorgio Valentini, David Sahner, Melissa Haendel, Peter N. Robinson, Carolyn Bramante, Justin Reese

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Aims: Studies suggest that metformin is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemics. We assessed if metformin is associated with reduced incidence of severe COVID-19 for patients with prediabetes or polycystic ovary syndrome (PCOS), common diseases that increase the risk of severe COVID-19. Methods: This observational, retrospective study utilized EHR data from 52 hospitals for COVID-19 patients with PCOS or prediabetes treated with metformin or levothyroxine/ondansetron (controls). After balancing via inverse probability score weighting, associations with COVID-19 severity were assessed by logistic regression. Results: In the prediabetes cohort, when compared to levothyroxine, metformin was associated with a significantly lower incidence of COVID-19 with “mild-ED” or worse (OR [95% CI]: 0.636, [0.455–0.888]) and “moderate” or worse severity (0.493 [0.339–0.718]). Compared to ondansetron, metformin was associated with lower incidence of “mild-ED” or worse severity (0.039 [0.026–0.057]), “moderate” or worse (0.045 [0.03–0.069]), “severe” or worse (0.183 [0.077–0.431]), and “mortality/hospice” (0.223 [0.071–0.694]). For PCOS, metformin showed no significant differences in severity compared to levothyroxine, but was associated with a significantly lower incidence of “mild-ED” or worse (0.101 [0.061–0.166]), and “moderate” or worse (0.094 [0.049–0.18]) COVID-19 outcome compared to ondansetron. Conclusions: Metformin use is associated with less severe COVID-19 in patients with prediabetes or PCOS.

Original languageEnglish (US)
Article number110157
JournalDiabetes Research and Clinical Practice
StatePublished - Dec 2022

Bibliographical note

Funding Information:
This work was supported by NCATS U24 TR002306. Additionally, Justin T. Reese and Nomi L. Harris were supported by the Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231; Justin T. Reese, Melissa Haendel, Peter N. Robinson, and Nomi L. Harris were supported by National Human Genome Research Institute awards 7RM1HG010860-02 and 2R24-OD011883-10A1; Adnin Zaman was supported by NIH NIDDK grant F32 DK123878. Melissa Haendel was supported by the Marsico Family at the University of Colorado Anschutz Medical Campus; Elena Casiraghi and Giorgio Valentini were supported by Università degli Studi di Milano, Piano di sviluppo di ricerca, grant 2015-17 PSR2015-17.

Funding Information:
The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave ( and supported by CD2H - The National COVID Cohort Collaborative (N3C) IDeA CTR Collaboration 3U24TR002306-04S2 NCATS U24 TR002306, DUR: RP-7BE1AC. This research was possible because of the patients whose information is included within the data from participating organizations ( and the organizations and scientists ( who have contributed to the on-going development of this community resource 27 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the N3C program. The N3C data transfer to NCATS is performed under a Johns Hopkins University Reliance Protocol #IRB00249128 or individual site agreements with NIH. The N3C Data Enclave is managed under the authority of the NIH; information can be found at

Publisher Copyright:
© 2022


  • COVID-19
  • Glycemia
  • Metformin
  • Polycystic ovary syndrome
  • Prediabetes


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