Faculty of Medicine and Health Sciences, University of Nottingham, UK.
Br J Clin Pharmacol. 2022 Jun;88(6):2642-2656. doi: 10.1111/bcp.15258. Epub 2022 Feb 23.
The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in patients with COVID-19 and DM and may be a potential candidate for drug repurposing. We aimed to investigate the effects of metformin on outcomes in patients with COVID-19 and DM.
Databases (PubMed, Scopus, Web of Science, EMBASE, Clinicaltrials.gov and Cochrane library) were searched up to 10 April 2021 for studies reporting data on metformin use in COVID-19 patients with DM. The risk of bias was assessed using the Newcastle-Ottawa scale. Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality reported as odds ratio (OR). A random-effects meta-analysis was carried out on both unadjusted and adjusted ORs. This study is registered with PROSPERO, CRD42020221842.
In total, 2 916 231 patients from 32 cohort studies were included in the quantitative and qualitative synthesis. The meta-analysis showed that metformin was significantly associated with lower mortality in COVID-19 patients with DM in both unadjusted (OR 0.61 [95% confidence interval: 0.53-0.71], P < .00001, I = 70%) and adjusted (OR 0.78 [95% confidence interval: 0.69-0.88], P < .00001, I = 67%) models.
Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a possible role of its use. However, robust randomised trials are needed to thoroughly assess its use.
新冠疫情是一场全球公共卫生紧急事件，糖尿病（DM）患者受到的影响不成比例，表现出更严重的结局。最近的研究表明，二甲双胍可改善 COVID-19 合并 DM 患者的结局，可能是药物再利用的潜在候选药物。我们旨在研究二甲双胍对 COVID-19 合并 DM 患者结局的影响。
截至 2021 年 4 月 10 日，我们检索了 PubMed、Scopus、Web of Science、EMBASE、Clinicaltrials.gov 和 Cochrane 图书馆等数据库，以获取报告二甲双胍治疗 COVID-19 合并 DM 患者数据的研究。使用纽卡斯尔-渥太华量表评估偏倚风险。使用 GRADE 方法评估证据确定性。主要结局是报告的死亡率，采用比值比（OR）表示。对未调整和调整后的 OR 进行了随机效应荟萃分析。本研究已在 PROSPERO 注册，CRD42020221842。
共有 32 项队列研究的 2916231 例患者纳入定量和定性综合分析。荟萃分析表明，二甲双胍与 COVID-19 合并 DM 患者的死亡率显著相关，无论是未调整（OR 0.61 [95%置信区间：0.53-0.71]，P<0.00001，I 2 =70%）还是调整后模型（OR 0.78 [95%置信区间：0.69-0.88]，P<0.00001，I 2 =67%）。
COVID-19 合并 DM 患者不良结局可归因于血糖控制不佳和免疫反应减弱。二甲双胍具有多种改善 DM 患者结局的作用，我们的研究结果强调了其可能的作用。但是，需要进行严格的随机对照试验以全面评估其使用情况。
