Abstract
Objectives: 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. Methods: 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”). Results: 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. Conclusion: 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) via 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of increased acidosis and lactic acidosis in patients with more severe Covid-19 disease remind that metformin should be withdrawn in patients with hypoxaemia or acute renal disease.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.
Highlights
Covid-19 has infected millions of people world wide (Covid live, 2021), and it is well recognised that people with type 2 diabetes are more susceptible to Covid19 infection and worse outcomes (Apicella et al, 2020; Feldman et al, 2020)
Metformin was associated with reduced risk of death within 28 d 0.65 (0.45, 0.93) More (p = 0.004) life-threatening complications in 56 metformin users (29%) vs. 54 non-metformin users (7.4%), with higher risk of disease progression during hospitalization [OR 3.964 (1.034, 15.194), p = 0.045] No effect of metformin (N = 678) vs. non-metformin (N = 535) on 30 day mortality [HR 1.65 (0.71, 3.86), p = 0.247]
People with diabetes are at a markedly increased risk of adverse outcomes related to Covid-19 infection
Summary
Covid-19 has infected millions of people world wide (Covid live, 2021), and it is well recognised that people with type 2 diabetes are more susceptible to Covid infection and worse outcomes (Apicella et al, 2020; Feldman et al, 2020). A growing evidence base of real-world studies has explored the effects of diabetes and metformin, the most commonly used treatment in type 2 diabetes, on the clinical course of Covid-19. We have reviewed the current literature on this topic and summarised the latest data on the impacts of diabetes and metformin on Covid-19 outcomes to derive pragmatic proposals for when to continue or withdraw treatment with metformin
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