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Review
. 2022 Jul;48(4):101359.
doi: 10.1016/j.diabet.2022.101359. Epub 2022 May 31.

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

Nicolas Wiernsperger  1 , Abdallah Al-Salameh  2 , Bertrand Cariou  3 , Jean-Daniel Lalau  4
Affiliations
Review

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

Nicolas Wiernsperger et al. Diabetes Metab. 2022 Jul.

Abstract

Since the outbreak of Covid-19, several observational studies on diabetes and Covid-19 have reported a favourable association between metformin and Covid-19-related outcomes in patients with type 2 diabetes mellitus (T2DM). This is not surprising since metformin affects many of the pathophysiological mechanisms implicated in SARS-CoV-2 immune response, systemic spread and sequelae. A comparison of the multifactorial pathophysiological mechanisms of Covid-19 progression with metformin's well-known pleiotropic properties suggests that the treatment of patients with this drug might be particularly beneficial. Indeed, metformin could alleviate the cytokine storm, diminish virus entry into cells, protect against microvascular damage as well as prevent secondary fibrosis. Although our in-depth analysis covers many potential metformin mechanisms of action, we want to highlight more particularly its unique microcirculatory protective effects since worsening of Covid-19 disease clearly appears as largely due to severe defects in the structure and functioning of microvessels. Overall, these observations confirm that metformin is a unique, pleiotropic drug that targets many of Covid-19's pathophysiology processes in a diabetes-independent manner.

Keywords: Covid-19; Death; Inflammation; Metformin; Microcirculation; Type 2 diabetes.

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Conflict of interest statement

Declaration of Competing Interest NW declares no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported. AAS reports personal fees from AstraZeneca, Lilly, and Novo Nordisk. BC reports BC reports grants and personal fees from Amgen, personal fees from AstraZeneca, personal fees from Akcea, personal fees from Genfit, personal fees from Gilead, personal fees from Eli Lilly, personal fees from Novo Nordisk, personal fees from MSD, grants and personal fees from Sanofi, and grants and personal fees from Regeneron. JDL reports personal fees from AstraZeneca, Brothier, Lilly, MSD, Novo Nordisk, Pfizer, and Sanofi.

Figures

Fig. 1
Fig. 1
AMPK's multifaceted involvement as a major mechanism in the physiological and biochemical processes of multifactorial diseases (e.g. Covid-19). AMP, adenosine monophosphate; AMPK, 5′-AMP-activated protein kinase; LKB1: serine–threonine liver kinase B1; H2S, hydrogen sulphide; ER, endoplasmic reticulum; HIF-1, hypoxia-inducible factor 1; MMP, matrix metalloproteinase.
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