General Internal Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Genomics Center, University of Minnesota, Minneapolis, Minnesota, USA.
Clin Infect Dis. 2024 Aug 16;79(2):354-363. doi: 10.1093/cid/ciae159.
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%.
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.
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.
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.
NCT04510194.
二甲双胍对包括严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在内的 RNA 病毒具有抗病毒活性。其机制似乎是通过靶向宿主雷帕霉素机制靶点来抑制蛋白翻译。在 COVID-OUT 针对门诊 2019 年冠状病毒病（COVID-19）的随机试验中，二甲双胍将 28 天内住院/死亡的几率降低了 58%，14 天内急诊就诊/住院/死亡的几率降低了 42%，10 个月内长期 COVID 的几率降低了 42%。
COVID-OUT 是一项 2×3 随机、安慰剂对照、双盲试验，评估了二甲双胍、氟伏沙明和伊维菌素；999 名参与者在第 1 天（n=945）、第 5 天（n=871）和第 10 天（n=775）自行采集前鼻拭子。使用逆转录定量聚合酶链反应定量病毒载量。
与安慰剂相比，二甲双胍使 SARS-CoV-2 病毒载量平均降低 3.6 倍（-0.56 log10 拷贝/mL；95%置信区间[CI]，-1.05 至 -.06；P=0.027）。与安慰剂相比，第 5 天或第 10 天接受二甲双胍治疗的患者中，病毒载量检测不到的可能性更低（比值比[OR]，0.72；95%CI，0.55 至 0.94）。二甲双胍（3.28%）比安慰剂（5.95%）发生病毒反弹（定义为第 10 天病毒载量高于第 5 天）的频率更低（OR，0.68；95%CI，0.36 至 1.29）。二甲双胍的效果在各亚组中一致，并随时间推移而增加。伊维菌素和氟伏沙明均未显示优于安慰剂的效果。
在这项针对门诊 SARS-CoV-2 治疗的随机、安慰剂对照试验中，二甲双胍显著降低了 SARS-CoV-2 病毒载量，这可能解释了该试验中的临床获益。二甲双胍具有其他与 COVID-19 病理生理学相关的多效性作用。
NCT04510194。
