{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:05:41Z","timestamp":1783933541360,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,9]]},"group-title":"Epidemiology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Allergy and Infectious Diseases","award":["1K01AI182501"],"award-info":[{"award-number":["1K01AI182501"]}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"crossref","award":["R01131542"],"award-info":[{"award-number":["R01131542"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["U54 GM115458"],"award-info":[{"award-number":["U54 GM115458"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Metformin is one of the most commonly prescribed medications for individuals with diabetes and may provide protection against long-term sequelae of COVID-19.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated a retrospective cohort of individuals in the National Clinical Cohort Collaborative with type 2 diabetes mellitus and COVID-19 who were prescribed metformin or a dipeptidyl peptidase-4 inhibitor (DPP4i) at least 30 days before the onset of acute COVID-19 between October 1, 2021, and November 15, 2023. We compared the 12-month cumulative incidence of Long COVID diagnosis (ICD-10 U09.9: Post COVID-19 condition, unspecified), probable Long COVID (based on a model-derived phenotype), and mortality between individuals prescribed metformin vs. DPP4i. We applied Super Learner and targeted maximum likelihood estimation to obtain risk ratios while adjusting for covariates of interest.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In our sample of 53,332 individuals with type 2 diabetes and COVID-19, we found that metformin prescription was associated with a lower risk of all-cause mortality after COVID-19 (adjusted risk ratio [aRR] 0.61, 95% CI 0.51, 0.73). We also observed that metformin users, compared to DPP4i users, had a slightly lower risk of probable Long COVID (aRR 0.87, 95% CI 0.81, 0.94) but did not detect a significant relationship with Long COVID diagnosis (aRR 0.90, 95% CI 0.68, 1.20), although we observed similar point estimates across Long COVID outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings support the hypothesis that metformin prescription during acute COVID-19 may be associated with lower mortality among adults with diabetes. These analyses also provide modest evidence of a protective association against Long COVID in adults with diabetes, although estimates were imprecise.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.06.26357398","type":"posted-content","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:20:24Z","timestamp":1783621224000},"source":"Crossref","is-referenced-by-count":0,"title":["Metformin and Severe Post-COVID-19 Outcomes Among Individuals with Diabetes Mellitus"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-0008","authenticated-orcid":false,"given":"Zachary","family":"Butzin-Dozier","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Chiun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunwen","family":"Ji","sequence":"additional","affiliation":[{"name":"School of Public Health, University of California, Berkeley, Berkeley, CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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