We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.
- Authors
Bramante, Carolyn T; Beckman, Kenneth B; Mehta, Tanvi; Karger, Amy B; Odde, David J; Tignanelli, Christopher J; Buse, John B; Johnson, Darrell M; Watson, Ray H B; Daniel, Jerry J; Liebovitz, David M; Nicklas, Jacinda M; Cohen, Ken; Puskarich, Michael A; Belani, Hrishikesh K; Siegel, Lianne K; Klatt, Nichole R; Anderson, Blake; Hartman, Katrina M; Rao, Via
- Abstract
Background Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 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%. Methods COVID-OUT was a 2 × 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. Results The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (−0.56 log10 copies/mL; 95% confidence interval [CI], −1.05 to −.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. Conclusions 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. Clinical Trials Registration NCT04510194.
- Subjects
MORTALITY prevention; METFORMIN; VIRAL load; EMERGENCY room visits; HOSPITAL care; FLUVOXAMINE; REVERSE transcriptase polymerase chain reaction; DESCRIPTIVE statistics; ANTIVIRAL agents; RACE; ODDS ratio; DRUG efficacy; MACROLIDE antibiotics; CONFIDENCE intervals; COVID-19
- Publication
Clinical Infectious Diseases, 2024, Vol 79, Issue 2, p354
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciae159