Metformin Might Inhibit Virus through Increasing Insulin Sensitivity

Chen, Yong; Gu, Feng; Guan, Jian-Long

doi:10.4103/0366-6999.223856

Cited by 29 publications

(26 citation statements)

References 5 publications

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“…Metformin, a blood glucose lowering geroprotector that activates 5'AMP-activated protein kinase (AMPK) and inhibits the mTOR pathway, has also been suggested as a possible drug to combat severe SARS-CoV-2 infection in older people. In addition to its potential insulin-sensitizing antiviral effect [164], metformin confers a myriad of anti-aging benefits including improving mitochondrial metabolism, decreasing inflammatory cytokines, protecting against genomic instability and decreasing cellular senescence [165], which may bolster the aging body's resistance to COVID-19. Results from the ongoing Targeting Aging with MEtformin (TAME) clinical trials and others should reveal whether these anti-aging drugs are protective against SARS-CoV-2 infection [165,166].…”

Section: Geroprotectors To Improve Immunitymentioning

confidence: 99%

Why does COVID-19 disproportionately affect older people?

Mueller

McNamara

Sinclair

2020

Aging

830

763

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The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient's age. Adults over 65 years of age represent 80% of hospitalizations and have a 23-fold greater risk of death than those under 65. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea, and from there the disease can progress to acute respiratory distress syndrome, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes and obesity increase the chances of fatal disease, but they alone do not explain why age is an independent risk factor. Here, we present the molecular differences between young, middle-aged and older people that may explain why COVID-19 is a mild illness in some but life-threatening in others. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase the survival of older people, not simply by inhibiting the virus, but by restoring patients' ability to clear the infection and effectively regulate immune responses.

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Section: Geroprotectors To Improve Immunitymentioning

confidence: 99%

Why does COVID-19 disproportionately affect older people?

Mueller

McNamara

Sinclair

2020

Aging

830

763

View full text Add to dashboard Cite

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“…Metformin, the first-line therapy for T2DM with undisputed efficacy and safety and additional antineoplastic, antiaging, anti-inflammatory, immunomodulatory, cardio-, neuro-, hepato-, and nephroprotective actions [275,276], has been proposed as a multi-action protection drug candidate for COVID-19 [277][278][279][280][281][282][283], particularly due to its strong systemic reparatory and modulatory mechanisms. While its effects on RAAS seem to be neutral, lung injury can be efficiently prevented and relieved by metformin, specially by the promotion of microvascular repairing actions [284][285][286][287][288][289], and has also exhibited antiviral activity, enhanced lymphocyte B function and enhanced innate immunity [290][291][292][293][294]. Conversely, metformin has formal contraindication for severe conditions due to the risk of lactic acidosis [295].…”

Section: Of Minor Relevancementioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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“…Addition of a phosphate group causes conformational and functional changes that could theoretically lead to a decrease in SARS-CoV-2 binding to the receptor [25]. However, upregulation of ACE2 diminishes the deleterious effects of the proinflammatory cascade induced by the renin-angiotensin-aldosterone system (RAS) [26].…”

Section: Use Of Oral Glucose-lowering Medications Metforminmentioning

confidence: 99%

Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature

et al. 2020

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The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.

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Metformin Might Inhibit Virus through Increasing Insulin Sensitivity

Cited by 29 publications

References 5 publications

Why does COVID-19 disproportionately affect older people?

Why does COVID-19 disproportionately affect older people?

Repurposing existing drugs for COVID-19: an endocrinology perspective

Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature

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