Chowdhury Saifur R, Islam Nazmul, Zhou Qi, Hasan Md Kamrul, Chowdhury Mahmudur Rahman, Siemieniuk Reed Ac, Agarwal Arnav, Brignardello-Petersen Romina, Agoritsas Thomas, Olav Vandvik Per, Zeraatkar Dena, Guyatt Gordon
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Evidence-based Medicine Centre, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansun, China.
BMJ Med. 2025 May 21;4(1):e001126. doi: 10.1136/bmjmed-2024-001126. eCollection 2025.
To summarise the effects of metformin on covid-19 to inform a World Health Organization (WHO) clinical practice guideline.
Systematic review and meta-analysis.
As part of a living systematic review and network meta-analysis of drug treatments for covid-19 (covid-19 LNMA), a search was performed of the WHO covid-19 database, six Chinese databases, and the Epistemonikos Foundation's Living Overview of the Evidence covid-19 Repository (covid-19 L-OVE).
Randomised controlled trials that compared metformin with placebo in patients with acute covid-19 infection.
Frequentist pairwise meta-analyses were performed using the restricted maximum likelihood random effects model. The effects of interventions on selected outcomes were summarised using risk ratios, risk difference, and mean difference when appropriate, along with their corresponding 95% confidence intervals (CIs). To estimate absolute effects, the control arm event rate was used as the baseline risk. The risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool and the certainty of evidence using the GRADE (grading of recommendations assessment, development and evaluation) approach, with the minimally important difference in effect as the threshold.
Three randomised controlled trials of 1869 patients were included; one study provided long term follow-up on long covid. Metformin might have little or no impact on mortality (risk ratio 0.76, 95% CI 0.30 to 1.90; risk difference 3 fewer per 1000, 95% CI 8 fewer to 11 more; low certainty). The effects of metformin on admission to hospital because of covid-19 remain uncertain (risk ratio 0.74, 95% CI 0.28 to 1.95; risk difference 15 fewer per 1000, 95% CI 42 fewer to 55 more; very low certainty). Metformin results in little or no difference in adverse effects leading to discontinuation (risk difference 0.2 more per 1000, 95% CI 2.7 fewer to 3.1 more; high certainty). Metformin might decrease the development of long covid (risk ratio 0.6, 95% CI 0.4 to 0.9; risk difference 41 fewer per 1000, 95% CI 62 fewer to 10 fewer; low certainty). However, the effect is based on a single trial of 1126 patients, which has a high risk of bias owing to missing data, and nearly half of the participants were unvaccinated.
Current evidence based on randomised trials suggests no significant effect of metformin on acute clinical outcomes in patients with non-severe covid-19. Metformin might reduce the incidence of long covid when used to treat patients with non-severe acute covid-19 infection, but this was suggested by low certainty evidence from a single trial.
总结二甲双胍对新冠病毒病（COVID-19）的影响，以为世界卫生组织（WHO）临床实践指南提供参考。
系统评价和荟萃分析。
作为一项关于COVID-19药物治疗的动态系统评价和网状荟萃分析（COVID-19 LNMA）的一部分，检索了WHO的COVID-19数据库、六个中文数据库以及Epistemonikos基金会的COVID-19证据动态综述库（COVID-19 L-OVE）。
比较二甲双胍与安慰剂用于急性COVID-19感染患者的随机对照试验。
采用受限最大似然随机效应模型进行频率学派的成对荟萃分析。干预措施对选定结局的影响在适当情况下用风险比、风险差和均值差进行总结，并给出相应的95%置信区间（CI）。为估计绝对效应，将对照组事件发生率用作基线风险。采用对Cochrane偏倚风险2.0工具的修改版评估纳入研究的偏倚风险，并采用GRADE（推荐分级评估、制定与评价）方法评估证据的确定性，以效应的最小重要差异为阈值。
纳入三项针对1869例患者的随机对照试验；一项研究提供了对新冠后状况的长期随访。二甲双胍可能对死亡率几乎没有影响或无影响（风险比0.76，95%CI 0.30至1.90；风险差每1000人少3例，95%CI少8例至多11例；低确定性）。二甲双胍对因COVID-19住院的影响仍不确定（风险比0.74，95%CI 0.28至1.95；风险差每1000人少15例，95%CI少42例至多55例；极低确定性）。二甲双胍导致因不良反应停药的差异很小或无差异（风险差每1000人多0.2例，95%CI少2.7例至多3.1例；高确定性）。二甲双胍可能会降低新冠后状况的发生（风险比0.6，95%CI 0.4至0.9；风险差每1000人少41例，95%CI少62例至少10例；低确定性）。然而，该效应基于一项针对1126例患者的单一试验，由于数据缺失，该试验存在较高的偏倚风险，且近一半参与者未接种疫苗。
基于随机试验的现有证据表明，二甲双胍对非重症COVID-19患者的急性临床结局无显著影响。在用于治疗非重症急性COVID-19感染患者时，二甲双胍可能会降低新冠后状况的发生率，但这是由一项单一试验的低确定性证据所提示的。
