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The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations\/death through 28 days by 58%, of emergency department visits\/hospitalizations\/death through 14 days by 42%, and of long COVID through 10 months by 42%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>COVID-OUT was a 2 \u00d7 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (\u22120.56 log10 copies\/mL; 95% confidence interval [CI], \u22121.05 to \u2212.06; P = .027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials Registration<\/jats:title>\n                    <jats:p>NCT04510194.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciae159","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T20:25:14Z","timestamp":1713299114000},"page":"354-363","source":"Crossref","is-referenced-by-count":49,"title":["Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5858-2080","authenticated-orcid":false,"given":"Carolyn T","family":"Bramante","sequence":"first","affiliation":[{"name":"General Internal Medicine, University of Minnesota , Minneapolis, Minnesota , 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