Bailey Clifford J, Gwilt Mike
Life and Health Sciences, Aston University, Birmingham, United Kingdom.
Front Pharmacol. 2022 Mar 9;13:784459. doi: 10.3389/fphar.2022.784459. eCollection 2022.
Pre-existing or new diabetes confers an adverse prognosis in people with Covid-19. We reviewed the clinical literature on clinical outcomes in metformin-treated subjects presenting with Covid-19. Structured PubMed search: metformin AND [covid (ti) OR covid-19 (ti) OR covid19 (ti) OR coronavirus (ti) OR SARS-Cov2 (ti)], supplemented with another PubMed search: "diabetes AND [covid OR covid-19 OR covid19 OR coronavirus (i) OR SARS-Cov2 (ti)]" (limited to "Clinical Study", "Clinical Trial", "Controlled Clinical Trial", "Meta-Analysis", "Observational Study", "Randomized Controlled Trial", "Systematic Review"). The effects of metformin on the clinical course of Covid-19 were evaluated in retrospective analyses: most noted improved clinical outcomes amongst type 2 diabetes patients treated with metformin at the time of hospitalisation with Covid-19 infection. These outcomes include reduced admission into intensive care and reduced mortality in subgroups with versus without metformin treatment. The pleiotropic actions of metformin associated with lower background cardiovascular risk may mediate some of these effects, for example reductions of insulin resistance, systemic inflammation and hypercoagulability. Modulation by metformin of the cell-surface ACE2 protein (a key binding target for SARS-CoV 2 spike protein) the AMP kinase pathway may be involved. While pre-existing metformin treatment offers potentially beneficial effects and can be continued when Covid-19 infection is not severe, reports of increased acidosis and lactic acidosis in patients with more severe Covid-19 disease remind that metformin should be withdrawn in patients with hypoxaemia or acute renal disease. Prospective study of the clinical and metabolic effects of metformin in Covid-19 is warranted.
既往存在的或新发的糖尿病会使新冠肺炎患者的预后不良。我们回顾了关于接受二甲双胍治疗的新冠肺炎患者临床结局的临床文献。在PubMed进行结构化检索:二甲双胍 AND [新冠(主题)或2019冠状病毒病(主题)或新冠19(主题)或冠状病毒(主题)或严重急性呼吸综合征冠状病毒2(主题)],并补充另一项PubMed检索:“糖尿病 AND [新冠或2019冠状病毒病或新冠19或冠状病毒(主题)或严重急性呼吸综合征冠状病毒2(主题)]”(限于“临床研究”“临床试验”“对照临床试验”“荟萃分析”“观察性研究”“随机对照试验”“系统评价”)。在回顾性分析中评估了二甲双胍对新冠肺炎临床病程的影响:大多数研究指出,在因新冠肺炎感染住院时接受二甲双胍治疗的2型糖尿病患者中,临床结局有所改善。这些结局包括重症监护入院率降低以及在接受与未接受二甲双胍治疗的亚组中死亡率降低。二甲双胍的多效性作用与较低的背景心血管风险相关,可能介导了其中一些效应,例如胰岛素抵抗、全身炎症和高凝状态的降低。二甲双胍对细胞表面血管紧张素转换酶2蛋白(严重急性呼吸综合征冠状病毒2刺突蛋白的关键结合靶点)的调节可能涉及AMP激酶途径。虽然既往接受二甲双胍治疗可能具有潜在益处,且在新冠肺炎感染不严重时可以继续使用,但有报告称,在病情更严重的新冠肺炎患者中酸中毒和乳酸酸中毒增加,这提醒我们,对于低氧血症或急性肾疾病患者应停用二甲双胍。有必要对二甲双胍在新冠肺炎中的临床和代谢效应进行前瞻性研究。