REFERENCES
1 Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934.
2 Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708–20.
3 Jean S-S, Lee P-I, Hsueh P-R. Treatment options for COVID-19: The reality and challenges. J Microbiol Immunol Infect. 2020 Jun;53(3):436–43.
4 Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19). JAMA. 2020 Aug 25;324(8):782.
5     Marchetti P, Giannarelli R, di Carlo A, Navalesi R. Pharmacokinetic optimisation of oral hypoglycaemic therapy. Clin Pharmacokinet. 1991 Oct;21(4):308–17.
6     Spiller HA. Management of Antidiabetic Medications in Overdose. Drug Saf. 1998;19(5):411–24.
7   Gong L, Goswami S, Giacomini KM, Altman RB, Klein TE. Metformin pathways. Pharmacogenet Genomics. 2012 Nov;22(11):820–7.
8   Weinberg ED. ANTIMICROBIAL ACTIVITIES OF BIGUANIDES. Ann N Y Acad Sci. 1968 Mar;148(3 Diabetes Mell):587–600.
9   Ishida N. VIRUS INHIBITORY ACTIVITY OF BIGUANIDES AND RELATED COMPOUNDS. Ann N Y Acad Sci. 2006 Dec 16;130(1):460–8.
10   Yang JK, Feng Y, Yuan MY, Yuan SY, Fu HJ, Wu BY, et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006 Jun;23(6):623–8.
11     Zhu L, She Z-G, Cheng X, Qin J-J, Zhang X-J, Cai J, et al. Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes. Cell Metab. 2020 Jun;31(6):1068-1077.e3.
12   Iacobellis G, Penaherrera CA, Bermudez LE, Bernal Mizrachi E. Admission hyperglycemia and radiological findings of SARS-CoV2 in patients with and without diabetes. Diabetes Res Clin Pract. 2020 Jun;164:108185.
13   Zhang Y, Li H, Zhang J, Cao Y, Zhao X, Yu N, et al. The clinical characteristics and outcomes of patients with diabetes and secondary hyperglycaemia with coronavirus disease 2019: A single-centre, retrospective, observational study in Wuhan. Diabetes Obes Metab. 2020;22(8):1443–54.
14     Ilias I, Zabuliene L. Hyperglycemia and the novel Covid-19 infection: Possible pathophysiologic mechanisms. Med Hypotheses. 2020 Jun;139:109699.
15   Brufsky A. Hyperglycemia, hydroxychloroquine, and the COVID‐19 pandemic. J Med Virol. 2020 Jul 27;92(7):770–5.
16     Codo AC, Davanzo GG, Monteiro LB, Souza G, Muraro S, Carregari V, et al. Elevated Glucose Levels Favor Sars-Cov-2 Infection and Monocyte Response Through a Hif-1α/Glycolysis Dependent Axis. SSRN Electron J. 2020.
17   de Marcken M, Dhaliwal K, Danielsen AC, Gautron AS, Dominguez-Villar M. TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection. Sci Signal. 2019 Oct 29;12(605):eaaw1347.
18     Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 May 19;17(5):533–5.
19   Isabel I, Aguilera DV, Betancourt MO, Rodríguez LA, Betzabel S, Gallardo R, et al. Metformina : Uso clínico y actualización. 2019;87(1).
20     Bridges HR, Jones AJY, Pollak MN, Hirst J. Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J. 2014 Sep 15;462(3):475–87.
21 Matsuzaki S, Humphries KM. Selective Inhibition of Deactivated Mitochondrial Complex I by Biguanides. Biochemistry. 2015 Mar 24;54(11):2011–21.
22 Pietrocola F, Kroemer G. Metformin: a metabolic modulator. Oncotarget. 2017 Feb 7;8(6):9017–20.
23   Vial G, Detaille D, Guigas B. Role of Mitochondria in the Mechanism(s) of Action of Metformin. Front Endocrinol (Lausanne). 2019 May 7;10.
24   Pryor R, Cabreiro F. Repurposing metformin: an old drug with new tricks in its binding pockets. Biochem J. 2015 Nov 1;471(3):307–22.
25 Shafiei-Irannejad V, Samadi N, Salehi R, Yousefi B, Zarghami N. New insights into antidiabetic drugs: Possible applications in cancer treatment. Chem Biol Drug Des. 2017 Dec;90(6):1056–66.
26 Scheen AJ. Clinical Pharmacokinetics of Metformin. Clin. Pharmacokinet. 1996;30(5):359–71.
27   Markowicz-Piasecka M, Huttunen KM, Mateusiak L, Mikiciuk-Olasik E, Sikora J. Is Metformin a Perfect Drug? Updates in Pharmacokinetics and Pharmacodynamics. Curr Pharm Des. 2017 Jul 3;23(17).
28       Gilman Alfred Goodman, Brunton Laurence L., et al. The pharmacological basis of therapeutics: Goodman & Gilman’s. 13th ed. New York: McGraw-Hill Education; 2017. 1419 p. ISBN: 978-1-25-958474-9.
29   Kopecky C. Use of Noninsulin Antidiabetic Medications in Hospitalized Patients. Crit Care Nurs Clin North Am. 2013 Mar;25(1):39–53.
30   Sambol NC, Chiang J, Lin ET, Goodman AM, Liu CY, Benet LZ, et al. Kidney function and age are both predictors of pharmacokinetics of metformin. J Clin Pharmacol. 1995 Nov;35(11):1094–102.
31   Katulanda P, Dissanayake HA, Ranathunga I, Ratnasamy V, Wijewickrama PSA, Yogendranathan N, et al. Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. Diabetologia. 2020;63(8):1440–52.
32 Maniar K, Singh V, Moideen A, Bhattacharyya R, Chakrabarti A, Banerjee D. Inhalational supplementation of metformin butyrate: A strategy for prevention and cure of various pulmonary disorders. Biomed Pharmacother. 2018 Nov;107:495–506.
33 Cetin M, Sahin S. Microparticulate and nanoparticulate drug delivery systems for metformin hydrochloride. Drug Deliv. 2016 Oct;23(8):2796–805.
34 Berstein LM. Metformin: not only per os. Expert Rev Endocrinol Metab. 2018 Mar 4;13(2):63–5.
35 Menendez JA, Quirantes-Piné R, Rodríguez-Gallego E, Cufí S, Corominas-Faja B, Cuyàs E, et al. Oncobiguanides: Paracelsus’ law and nonconventional routes for administering diabetobiguanides for cancer treatment. Oncotarget. 2014 May 15;5(9):2344–8.
36   Nakhleh A, Shehadeh N. Interactions between antihyperglycemic drugs and the renin-angiotensin system: Putative roles in COVID-19. A mini-review. Diabetes Metab Syndr. 14(4):509–12.
37   Joven J, Menéndez J, Fernandez-Sender L, Espinel E, Rull A, Beltrán-Debón R, et al. Metformin: a cheap and well-tolerated drug that provides benefits for viral infections. HIV Med. 2013 Apr;14(4):233–40.
38   Chen Y, Gu F, Guan J-L. Metformin Might Inhibit Virus through Increasing Insulin Sensitivity. Chin Med J (Engl). 2018 Feb;131(3):376–7.
39 Yu J-W, Sun L-J, Zhao Y-H, Kang P, Yan B-Z. The effect of metformin on the efficacy of antiviral therapy in patients with genotype 1 chronic hepatitis C and insulin resistance. Int J Infect Dis. 2012 Jun;16(6):e436–41.
40   Khan IM, Malik BR, Randhawa FA, Butt NF, Malik U, Hamid S. Comparison of metformin and pioglitazone in achieving sustained virological response in chronic hepatitis C patients with insulin resistance: A quasi-experimental study. J Pak Med Assoc. 2017 Dec;67(12):1848–52.
41   Xun Y-H, Zhang Y-J, Pan Q-C, Mao R-C, Qin Y-L, Liu H-Y, et al. Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells. J Viral Hepat. 2014 Aug;21(8):597–603.
42   Singh S, Singh PK, Suhail H, Arumugaswami V, Pellett PE, Giri S, et al. AMP-Activated Protein Kinase Restricts Zika Virus Replication in Endothelial Cells by Potentiating Innate Antiviral Responses and Inhibiting Glycolysis. J Immunol. 2020 Apr 1;204(7):1810–24.
43   Lehrer S. Inhaled biguanides and mTOR inhibition for influenza and coronavirus (Review). World Acad Sci J. 2020 Mar 26.
44   Zhao X, Jiang Y, Zhao Y, Xi H, Liu C, Qu F, et al. Analysis of the susceptibility to COVID-19 in pregnancy and recommendations on potential drug screening. Eur J Clin Microbiol Infect Dis. 2020 Jul 23;39(7):1209–20.
45   Marcucci F, Romeo E, Caserta CA, Rumio C, Lefoulon F. Context-Dependent Pharmacological Effects of Metformin on the Immune System. Trends Pharmacol Sci. 2020 Mar;41(3):162–71.
46 Javeshghani S, Zakikhani M, Austin S, Bazile M, Blouin M-J, Topisirovic I, et al. Carbon Source and Myc Expression Influence the Antiproliferative Actions of Metformin. Cancer Res. 2012 Dec 1;72(23):6257–67.
47     Bost F, Decoux-Poullot A-G, Tanti JF, Clavel S. Energy disruptors: rising stars in anticancer therapy? Oncogenesis. 2016 Jan 18;5(1):e188–e188.
48 Song I-S, Han J, Lee HK. Metformin as an anticancer drug: A Commentary on the metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. J Diabetes Investig. 2015 Sep;6(5):516–8.
49 Zhou P-T, Li B, Liu F-R, Zhang M-C, Wang Q, Li Y-Y, et al. Metformin is associated with survival benefit in pancreatic cancer patients with diabetes: a systematic review and meta-analysis. Oncotarget. 2017 Apr 11;8(15):25242–50.
50   Pecinova A, Drahota Z, Kovalcikova J, Kovarova N, Pecina P, Alan L, et al. Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production. Oxid Med Cell Longev. 2017;2017:1–11.
51   Cuyàs E, Fernández-Arroyo S, Verdura S, García RÁ-F, Stursa J, Werner L, et al. Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism. Oncogene. 2018 Feb 23;37(7):963–70.
52   Qi B, Hu L, Zhu L, Shang L, Wang X, Liu N, et al. Metformin Attenuates Neurological Deficit after Intracerebral Hemorrhage by Inhibiting Apoptosis, Oxidative Stress and Neuroinflammation in Rats. Neurochem Res. 2017 Oct 29;42(10):2912–20.
53   Diaz A, Romero M, Vazquez T, Lechner S, Blomberg BB, Frasca D. Metformin improves in vivo and in vitro B cell function in individuals with obesity and Type-2 Diabetes. Vaccine. 2017 May;35(20):2694–700.
54   Jing Y, Wu F, Li D, Yang L, Li Q, Li R. Metformin improves obesity-associated inflammation by altering macrophages polarization. Mol Cell Endocrinol. 2018 Feb;461:256–64.
55   Saisho Y. Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect. Endocrine, Metab Immune Disord Targets. 2015 Aug 27;15(3):196–205.
56   Kang Z, Zeng J, Zhang T, Lin S, Gao J, Jiang C, et al. Hyperglycemia induces NF‐κB activation and MCP‐1 expression via downregulating GLP‐1R
57   Menegazzo L, Scattolini V, Cappellari R, Bonora BM, Albiero M, Bortolozzi M, et al. The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo. Acta Diabetol. 2018 Jun 15;55(6):593–601.
58     Karnewar S, Neeli PK, Panuganti D, Kotagiri S, Mallappa S, Jain N, et al. Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: Relevance in age-associated vascular dysfunction. Biochim Biophys Acta - Mol Basis Dis. 2018 Apr;1864(4):1115–28.
59   Lee M-S. Effect of mitochondrial stress on systemic metabolism. Ann N Y Acad Sci. 2015 Sep;1350(1):61–5.
60     Thomas HE, Zhang Y, Stefely JA, Veiga SR, Thomas G, Kozma SC, et al. Mitochondrial Complex I Activity Is Required for Maximal Autophagy. Cell Rep. 2018 Aug;24(9):2404-2417.e8.
61 Cameron AR, Logie L, Patel K, Erhardt S, Bacon S, Middleton P, et al. Metformin selectively targets redox control of complex I energy transduction. Redox Biol. 2018 Apr;14:187–97.
62   Jia J, Cheng J, Ni J, Zhen X. Neuropharmacological Actions of Metformin in Stroke. Curr Neuropharmacol. 2015 Jul 14;13(3):389–94.
63   Jin Q, Cheng J, Liu Y, Wu J, Wang X, Wei S, et al. Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental stroke. Brain Behav Immun. 2014 Aug;40:131–42.
64 Varjabedian L, Bourji M, Pourafkari L, Nader ND. Cardioprotection by Metformin: Beneficial Effects Beyond Glucose Reduction. Am J Cardiovasc Drugs. 2018 Jun 24;18(3):181–93.
65   Paiva M, Riksen NP, Davidson SM, Hausenloy DJ, Monteiro P, Gonçalves L, et al. Metformin Prevents Myocardial Reperfusion Injury by Activating the Adenosine Receptor. J Cardiovasc Pharmacol. 2009 May;53(5):373–8.
66   Soraya H, Clanachan AS, Rameshrad M, Maleki-Dizaji N, Ghazi-Khansari M, Garjani A. Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction. Eur J Pharmacol. 2014 Aug;737:77–84.
67 Soraya H, Rameshrad M, Mokarizadeh A, Garjani A. Metformin attenuates myocardial remodeling and neutrophil recruitment after myocardial infarction in rat. BioImpacts. 2017 Aug 15;5(1):3–8.
68 Anisimov VN. Metformin for cancer and aging prevention: is it a time to make the long story short? Oncotarget. 2015 Nov 24;6(37):39398–407.
69   Chung M-M, Nicol CJ, Cheng Y-C, Lin K-H, Chen Y-L, Pei D, et al. Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs. Exp Cell Res. 2017 Mar;352(1):75–83.
70       Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355–62.
71   Yu LL, Zhu M, Huang Y, Zhao YM, Wen JJ, Yang XJ, et al. Metformin relieves acute respiratory distress syndrome by reducing miR-138 expression. Eur Rev Med Pharmacol Sci. 2018;22(16):5355–63.
72   Alshawi A, Agius L. Low metformin causes a more oxidized mitochondrial NADH/NAD redox state in hepatocytes and inhibits gluconeogenesis by a redox-independent mechanism. J Biol Chem. 2019 Feb 22;294(8):2839–53.
73     Basu-Ray I, Almaddah Nk, Adeboye A, et al. Cardiac Manifestations Of Coronavirus (COVID-19) [Updated 2020 Aug 8]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020 Jan.
74   Li J, Benashski SE, Venna VR, McCullough LD. Effects of Metformin in Experimental Stroke. Stroke. 2010 Nov;41(11):2645–52.
75   Floyd JS, Wiggins KL, Christiansen M, Dublin S, Longstreth WT, Smith NL, et al. Case-control study of oral glucose-lowering drugs in combination with long-acting insulin and the risks of incident myocardial infarction and incident stroke. Pharmacoepidemiol Drug Saf. 2016 Feb;25(2):151–60.
76   Lexis CPH, van der Horst ICC, Lipsic E, Wieringa WG, de Boer RA, van den Heuvel AFM, et al. Effect of Metformin on Left Ventricular Function After Acute Myocardial Infarction in Patients Without Diabetes. JAMA. 2014 Apr 16;311(15):1526.
77   Hartman MHT, Prins JKB, Schurer RAJ, Lipsic E, Lexis CPH, van der Horst-Schrivers ANA, et al. Two-year follow-up of 4 months metformin treatment vs. placebo in ST-elevation myocardial infarction: data from the GIPS-III RCT. Clin Res Cardiol. 2017 Dec 28;106(12):939–46.
78   Higgins L, Palee S, Chattipakorn SC, Chattipakorn N. Effects of metformin on the heart with ischaemia-reperfusion injury: Evidence of its benefits from in vitro, in vivo and clinical reports. Eur J Pharmacol. 2019 Sep;858:172489.