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.

中文翻译：

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在一项 COVID-19 的随机、安慰剂对照临床试验中，二甲双胍对 SARS-CoV-2 病毒载量的良好抗病毒作用。


背景 二甲双胍对 RNA 病毒具有抗病毒活性，包括严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2）。其机制似乎是通过靶向雷帕霉素通路的宿主机制靶标来抑制蛋白质翻译。在 2019 年冠状病毒病 （COVID-19） 门诊患者的 COVID-OUT 随机试验中，二甲双胍将 28 天内住院/死亡的几率降低了 58%，急诊科就诊/住院/死亡 14 天内的几率降低了 42%，10 个月内的长期 COVID 几率降低了 42%。方法 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） 自行采集了前鼻拭子。使用逆转录定量聚合酶链反应对病毒载量进行定量。结果与安慰剂相比，二甲双胍的平均 SARS-CoV-2 病毒载量降低了 3.6 倍（-0.56 log10 拷贝/mL;95% 置信区间 [CI]，-1.05 至 -.06;P = .027）。与安慰剂组相比，接受二甲双胍治疗的患者在第 5 天或第 10 天检测病毒载量的可能性较小（比值比 [OR]，0.72;95% CI，0.55 至 .94）。病毒反弹，定义为第 10 天的病毒载量高于第 5 天，二甲双胍 （3.28%） 低于安慰剂 （5.95%;OR，0.68;95% CI，.36 至 1.29）。二甲双胍效应在亚组中是一致的，并且随着时间的推移而增加。伊维菌素和氟伏沙明均未显示出优于安慰剂的效果。结论 在这项 SARS-CoV-2 门诊治疗的随机、安慰剂对照试验中，二甲双胍显着降低了 SARS-CoV-2 病毒载量，这可能解释了该试验的临床益处。 二甲双胍具有多效性，具有与 COVID-19 病理生理学相关的其他作用。临床试验注册 NCT04510194.