Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial.

Autor: Bramante CT; General Internal Medicine, University of Minnesota, Minneapolis, MN., Beckman KB; Genomics Center, University of Minnesota, Minneapolis, MN., Mehta T; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN., Karger AB; Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN., Odde DJ; Department of Biomedical Engineering University of Minnesota, Minneapolis, MN., Tignanelli CJ; Department of Surgery, Medical School, University of Minnesota, Minneapolis, MN., Buse JB; Endocrinology, University of North Carolina, Chapel Hill, NC., Johnson DM; Genomics Center, University of Minnesota, Minneapolis, MN., Watson RHB; Genomics Center, University of Minnesota, Minneapolis, MN., Daniel JJ; Genomics Center, University of Minnesota, Minneapolis, MN., Liebovitz DM; General Internal Medicine, Northwestern University, Chicago, IL., Nicklas JM; General Internal Medicine, University of Colorado, Denver, CO., Cohen K; UnitedHealth Group, Optum Labs, Minnetonka, MN., Puskarich MA; Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN., Belani HK; Department of Medicine, Olive View - University of California, Los Angeles, CA., Siegel LK; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN., Klatt NR; Department of Surgery, Medical School, University of Minnesota, Minneapolis, MN., Anderson B; Atlanta Veterans Affairs Medical Center, Atlanta, Georgia; Department of Medicine, Emory University School of Medicine, Atlanta, GA., Hartman KM; General Internal Medicine, University of Minnesota, Minneapolis, MN., Rao V; General Internal Medicine, University of Minnesota, Minneapolis, MN., Hagen AA; General Internal Medicine, University of Minnesota, Minneapolis, MN., Patel B; General Internal Medicine, University of Minnesota, Minneapolis, MN., Fenno SL; General Internal Medicine, University of Minnesota, Minneapolis, MN., Avula N; General Internal Medicine, University of Minnesota, Minneapolis, MN., Reddy NV; General Internal Medicine, University of Minnesota, Minneapolis, MN., Erickson SM; General Internal Medicine, University of Minnesota, Minneapolis, MN., Fricton RD; General Internal Medicine, Northwestern University, Chicago, IL., Lee S; General Internal Medicine, Northwestern University, Chicago, IL., Griffiths G; General Internal Medicine, University of Minnesota, Minneapolis, MN., Pullen MF; Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, MN., Thompson JL; Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN., Sherwood N; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN., Murray TA; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN., Rose MR; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN., Boulware DR; Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, MN., Huling JD; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN.
Jazyk: angličtina
Zdroj: MedRxiv : the preprint server for health sciences [medRxiv] 2023 Jun 07. Date of Electronic Publication: 2023 Jun 07.
DOI: 10.1101/2023.06.06.23290989
Abstrakt: Current antiviral treatment options for SARS-CoV-2 infections are not available globally, cannot be used with many medications, and are limited to virus-specific targets. 1-3 Biophysical modeling of SARS-CoV-2 replication predicted that protein translation is an especially attractive target for antiviral therapy. 4 Literature review identified metformin, widely known as a treatment for diabetes, as a potential suppressor of protein translation via targeting of the host mTor pathway. 5 In vitro, metformin has antiviral activity against RNA viruses including SARS-CoV-2. 6,7 In the COVID-OUT phase 3, randomized, placebo-controlled trial of outpatient treatment of COVID-19, metformin had a 42% reduction in ER visits/hospitalizations/death through 14 days; a 58% reduction in hospitalizations/death through 28 days, and a 42% reduction in Long COVID through 10 months. 8,9 Here we show viral load analysis of specimens collected in the COVID-OUT trial that the mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (-0.56 log 10 copies/mL; 95%CI, -1.05 to -0.06, p=0.027) while there was no virologic effect for ivermectin or fluvoxamine vs placebo. The metformin effect was consistent across subgroups and with emerging data. 10,11 Our results demonstrate, consistent with model predictions, that a safe, widely available, 12 well-tolerated, and inexpensive oral medication, metformin, can be repurposed to significantly reduce SARS-CoV-2 viral load.
Databáze: MEDLINE