{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:12:34Z","timestamp":1792131154562,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013281","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000}}],"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/WT"],"award-info":[{"award-number":["106680\/WT"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec018\">\n<jats:title>Background<\/jats:title>\n<jats:p>Despite dengue being a major public health problem, there are no antiviral or adjunctive treatments for the disease. Novel therapeutics are needed, particularly for patients at high risk of severe disease, including those living with obesity. Metformin reduces dengue viral replication in vitro through AMPK activation and may also have beneficial immunomodulatory effects.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec019\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted an open label trial at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, enrolling 120 patients with dengue and obesity (60 treatment arm, 60 control arm receiving standard of care only). Within the treatment arm, the first 10 patients were prescribed low dose metformin, and the remaining 50 patients received weight-based dosing of 1-1.5g\/day. The primary outcome was the number of adverse events (AEs), and secondary outcomes were clinical and laboratory parameters, including fever clearance time, platelet nadir, percentage of haematocrit change from baseline, maximum creatinine and highest AST\/ALT, and the kinetics of plasma viraemia and NS1 antigenaemia.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec020\">\n<jats:title>Results<\/jats:title>\n<jats:p>The majority of patients in both groups had dengue with warning signs. Six patients in the metformin group and 5 controls developed dengue shock syndrome, and no patients died. There were more AEs recorded in the metformin treated group than in the control group (mean\u00b1SD: 15\u2009\u00b1\u20094 vs. 11\u2009\u00b1\u20096), particularly the high-dose metformin group (15\u2009\u00b1\u20095). Twenty-five patients (42%) had to stop the study drug due to AEs, including severe diarrhea (n\u2009=\u200912), dengue shock (n\u2009=\u20095), increased lactate of &gt;3mmol\/L (n\u2009=\u20094), hypoglycemia (n\u2009=\u20093), and persistent vomiting (n\u2009=\u20091). There were no clear differences in secondary outcomes between the two groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec021\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Metformin was poorly tolerated in patients with dengue, mainly due to gastrointestinal side effects. Metformin did not beneficially affect clinical evolution or virological parameters compared to supportive care alone. Our data does not support progression to larger phase 3 trials of metformin in patients with dengue.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec022\">\n<jats:title>Trial registration<\/jats:title>\n<jats:p>ClinicalTrials.gov: NCT04377451 (May 6<jats:sup>th<\/jats:sup>, 2020).<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0013281","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T18:01:58Z","timestamp":1751392918000},"page":"e0013281","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Safety and tolerability of metformin in overweight and obese patients with dengue: An open-label clinical trial (MeDO)"],"prefix":"10.1371","volume":"19","author":[{"given":"Nguyet","family":"Minh Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Thi Hoai 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