Doms № 1 -2022

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Doms № 1 -2022 (18-28 p)

Metformin Use Is Associated with Reduced Mortality in a Diverse Population With COVID-19 and Diabetes
Andrew B. Crouse, Tiffany Grimes, Peng Li, Matthew Might, Fernando Ovalle, Anath Shalev, 18-28

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Metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes
Andrew B Crouse, Tiffany Grimes, Peng Li , Matthew Might, Fernando Ovalle, Anath Shalev

Abstract

Background: Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking.
Methods: We conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19- positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression.

Results: The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans (OR 2.6; 95% CI 2.19-3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95% CI 1.64-2.28; p<0.0001), hypertension (OR 2.46; 95% CI 2.07-2.93; p<0.0001), and diabetes (OR 2.11; 95% CI 1.78-2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95% CI 2.11-6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity, and hypertension. Interestingly, we found that metformin treatment prior to diagnosis of COVID-19 was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95% CI 0.13-0.84; p=0.0210).

Conclusion: Thus, these results suggest that while diabetes is an independent risk factor for COVID-19-related mortality, this risk is dramatically reduced in subjects taking metformin prior to diagnosis of COVID-19, raising the possibility that metformin may provide a protective approach in this high-risk population.

Keywords: African-American; coronavirus disease-2019; diabetes; metformin; mortality.

  1. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. Jama (2020) 323(20):2052–9. doi: 10.1001/jama.2020.6775
  2. Palaiodimos L, Kokkinidis DG, Li W, Karamanis D, Ognibene J, Arora S, et al. Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York. Metabol: Clin Experiment (2020) 108:154262. doi: 10.1016/j.metabol.2020.154262
  3. CaiQ,ChenF,WangT,LuoF,LiuX,WuQ,etal.Obesityand COVID-19 Severity in a Designated Hospital in Shenzhen, China. Diabetes Care (2020) 43(7):1392– doi: 10.2337/ dc20-0576
  4. Chen Q, Zheng Z, Zhang C, Zhang X, Wu H, Wang J, et al. Clinical characteristics of 145 patients with corona virus disease 2019 (COVID-19) in Taizhou, Zhejiang, China. Infection (2020) 48(4):543–51. doi: 10.1007/ s15010-020-01432-5
  5. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama (2020) 323(11):1061–9. doi: 10.1001/jama.2020.1585
  6. Cariou B, Hadjadj S, Wargny M, Pichelin M, Al-Salameh A, Allix I, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia (2020) 63(8):1500– doi: 10.1007/ s00125-020-05180-x
  7. Scheen AJ, Marre M, Thivolet C. Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent re- ports. Diabetes Metab (2020) 46(4):265–71. doi: 10.1016/ j.diabet.2020.05.008
  8. Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and Mortality among Black Patients and White Patients with Covid-19. New Engl J Med (2020) 382(26):2534– doi: 10.1056/NEJMsa2011686
  9. Tai DBG, Shah A, Doubeni CA, Sia IG, Wieland ML. The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States. Clin Infect Dis Off Publ Infect Dis Soc A (2020). doi: 10.1093/cid/ciaa815
  10. Holmes L Jr, Enwere M, Williams J, Ogundele B, Chavan P, Piccoli T, et al. Black-White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges. Int J Environ Res Public Health (2020) 17 (12):4322. doi: 10.3390/ijerph17124322
  11. Golden SH, Yajnik C, Phatak S, Hanson RL, Knowler WC. Racial/ethnic differences in the burden of type 2 diabetes over the life course: a focus on the USA and India. Diabetologia (2019) 62(10):1751– doi: 10.1007/s00125-019-4968-0
  12. Bramante C, Ingraham N, Murray T, Marmor S, Hoversten S, Gronski J, et al. Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19. MedRxiv Prepr Server Health Sci (2020). doi: 10.1101/2020.06.19.20135095
  13. Tan MH, Alquraini H, Mizokami-Stout K, MacEachern M. Metformin: From Research to Clinical Practice. Endocrinol Metab Clinics North A (2016) 45 (4):819– doi: 10.1016/j. ecl.2016.06.008
  14. Luo P, Qiu L, Liu Y, Liu XL, Zheng JL, Xue HY, et al. Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis. Am J Trop Med Hygiene (2020) 103 (1):69–72. doi: 10.4269/ajtmh.20-0375
  15. Hariyanto TI, Kurniawan A. Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection. Obes Med (2020) 19:100290. doi: 10.1016/j.obmed.2020.100290
  16. Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, et al. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res (2016) 119(5):652– doi: 10.1161/CIRCRESAHA.116.308445
  17. Tsoyi K, Jang HJ, Nizamutdinova IT, Kim YM, Lee YS, Kim HJ, et al. Metformin inhibits HMGB1 release in LPS-treated
  1. Grant PJ. The effects of metformin on the fibrinolytic system in diabetic and non-diabetic subjects. Diabete Metabol (1991) 17(1 Pt 2):168–73.
  2. Xin G, Wei Z, Ji C, Zheng H, Gu J, Ma L, et al. Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release. Sci Rep (2016) 6:36222. doi: 10.1038/srep36222
  3. McFadyen JD, Stevens H, Peter K. The Emerging Threat of (Micro) Thrombosis in COVID-19 and Its Therapeutic Implications. Circ Res (2020) 127(4):571– doi: 10.1161/ CIRCRESAHA.120.317447
  4. Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood (2020) 135(23):2033–40. doi: 10.1182/ blood.2020006000
  5. Khan IH, Savarimuthu S, Leung MST, Harky A. The need to manage the risk of thromboembolism in COVID-19 patients. J Vasc Surg (2020) 72(3):799– 804. doi: 10.1016/j. jvs.2020.05.015
  6. Christiansen C, Johansen M, Christensen S, O’Brien JM, Tonnesen E, Sorensen H. Preadmission metformin use and mortality among intensive care patients with diabetes: a cohort study. Crit Care (2013) 17(5):R192. doi: 10.1186/ cc12886
  7. Zhu L, She ZG, Cheng X, Qin JJ, Zhang XJ, 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) 31(6):1068–77 e3. doi: 10.1016/ j.cmet.2020.04.021
  8. Mugabo Y, Li L, Renier G. The connection between C- reactive protein (CRP) and diabetic vasculopathy. Focus on preclinical findings. Curr Diabetes Rev (2010) 6(1):27–34. doi: 10.2174/157339910790442628
  9. Nogami K, Muraki I, Imano H, Iso H. Risk of disseminated intravascular coagulation in patients with type 2 diabetes mellitus: retrospective cohort study. BMJ Open (2017) 7(1):e013894. doi: 10.1136/bmjopen-2016-013894
  10. Yang L, Han Y, Nilsson-Payant BE, Gupta V, Wang P, Duan X, et al. A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids. Cell Stem Cell (2020) 27(1):125–36 e7. doi: 10.1016/j.stem.2020.06.015
  11. Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, Del Prato S. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol (2020) 8(9):782–92.

doi: 10.1016/ S2213-8587(20)30238-2

  1. Li J, Wang X, Chen J, Zuo X, Zhang H, Deng A. COVID-19 infection may cause ketosis and ketoacidosis. Diabetes Obes Metab (2020) 22(10):1935–41. doi: 10.1111/dom.14057
  2. Mauvais-Jarvis F. Aging, Male Sex, Obesity, and Metabolic Inflammation Create the Perfect Storm for COVID-19. Diabetes (2020) 69(9):1857–63. doi: 10.2337/dbi19-0023
  3. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol (2016) 16(10):626–38.

doi: 10.1038/ nri.2016.90

  1. Crouse A, Grimes T, Li P, Might M, Ovalle F, Shalev A. Metformin Use Is Associated with Reduced Mortality in a Diverse Population with Covid-19 and Diabetes. MedRxiv Prepr Server Health Sci (2020).

doi: 10.1101/2020.07.29.20164020

Originally published: Crouse AB, Grimes T, Li P, Might M, Ovalle F and Shalev A (2021) Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes. Front. Endocrinol. 11:600439.

doi: 10.3389/fendo.2020.600439
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