Doms № 5 -2022

The management of type 2 diabetes before, during and after Covid-19 infection: what is the evidence?
Leszek Czupryniak, Dror Dicker, Roger Lehmann, Martin Prázný, Guntram Schernthaner

DOI: https://doi.org/10.1186/s12933-021-01389-1

Abstract

Patients with Covid-19 place new challenges on the management of type 2 diabetes, including the questions of whether glucose-lowering therapy should be adjusted during infection and how to manage a return to normal care after resolution of Covid-19 symptoms. Due to the sudden onset of the pandemic, physicians have by necessity made such important clinical decisions in the absence of robust evidence or consistent guidelines. The risk to patients is compounded by the prevalence of cardiovascular disease in this population, which alongside diabetes is a major risk factor for severe disease and mortality in Covid-19. We convened as experts from the Central and Eastern European region to consider what advice we can provide in the setting of type 2 diabetes and Covid-19, considering the evidence before, during and after infection. We review recommendations that have been published to date, and consider the best available—but currently limited—evidence from large observational studies and the DARE-19 randomized control trial. Notably, we find a lack of guidance on restarting patients on optimal antidiabetic therapy after recovering from Covid-19, and suggest that this may provide an opportunity to optimize treatment and counter clinical inertia that predates the pandemic. Furthermore, we emphasize that optimization applies not only to glycaemic control, but other factors such as cardiorenal protection. While we look forward to the emergence of new evidence that we hope will address these gaps, in the interim we provide a perspective, based on our collective clinical experience, on how best to manage glucose-lowering therapy as patients with Covid-19 recover from their disease and return to normal care.

Keywords: Covid-19, type 2 diabetes, glucose-lowering therapy.

References

  1. Forde R, et al. The impact of the COVID-19 pandemic on people with diabetes and diabetes services: a pan-European survey of diabetes specialist nurses undertaken by the Foundation of European Nurses in Diabetes survey consortium. Diabet Med. 2021;83:e14498.
  2. Mantovani A, Byrne CD, Zheng M-H, Targher G. Diabetes as
    a risk factor for greater COVID-19 severity and in-hospital death: a meta-analysis of observational studies. Nutr Metab Cardiovasc Dis. 2020;30:1236–48.
  3. Corona G, et al. Diabetes is most important cause for mortality in COVID-19 hospitalized patients: systematic review and meta-analysis. Rev Endocr Metab Disord. 2021;22:275–96.
  4. de Jong M, Woodward M, Peters SAE. Diabetes and CO- VID-19–related mortality in women and men in the UK uenza/pneumonia and coronary heart disease. Diabetes Care. 2021;44:e22–4.
  5. Kumar A, et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab. Syndr. 2020;14:535–45.
  6. Myers AK, et al. Predictors of mortality in a multiracial urban cohort of persons with type 2 diabetes and novel coronavirus 19. J Diabetes. 2021;13:430–8.
  7. McGurnaghan SJ, et al. Risks of and risk factors for COVID-19
    disease in people with diabetes: a cohort study of the total population of Scotland. Lancet Diabetes Endocrinol. 2021;9:82–93.
  8. Sonmez A, et al. Clinical characteristics and outcomes of COVID-19 in patients with type 2 diabetes in Turkey: a nationwide study (TurCoviDia). J Diabetes. 2021;13:585–95.
  9. You JH, et al. Clinical outcomes of COVID-19 patients with type 2 diabetes: a population-based study in Korea. Endocrinol Metab. 2020;35:901–8.
  10. For the CORONADO investigators, et al. Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORO- NADO study. Diabetologia. 2021;64:778–94.
  11. Izzi-Engbeaya C, et al. Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study from three London teaching hospitals. BMJ Open Diabetes Res Care. 2021;9:e001858.
  12. Shrestha E, et al. Type 2 diabetes is associated with increased risk of critical respiratory illness in patients COVID-19 in a community hospital. Obes Med. 2021;22:100316.
  13. Chung MK, et al. COVID-19 and cardiovascular disease. Circ Res. 2021;128:1214–36.
  14. Sun B, Huang S, Zhou J. Perspectives of antidiabetic drugs in diabetes with coronavirus infections. Front Pharmacol. 2021;11:592439.
  15. Lim S, Bae JH, Kwon H-S, Nauck MA. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol. 2021;17:11–30.
  16. Korytkowski M, et al. A pragmatic approach to inpatient diabetes management during the COVID-19 pandemic. J Clin Endocrinol Metab. 2020;105:3076–87.
  17. Koliaki C, et al. Clinical management of diabetes mellitus in the era of COVID-19: practical issues, peculiarities and concerns. J Clin Med. 2020;9:2288.
  18. Katulanda P, et al. Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature. Diabetologia. 2020;63:1440–52.
  19. Hartmann-Boyce J, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020;43:1695–703.
  20. Futatsugi H, et al. Blood glucose control strategy for type 2 diabetes patients with COVID-19. Front Cardiovasc Med. 2020;7:593061.
  21. Bornstein SR, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020;8:546–50.
  22. Schernthaner G, et al. Worldwide inertia to the use of cardio- renal protective glucose-lowering drugs (SGLT2i and GLP-1 RA) in high-risk patients with type 2 diabetes. Cardiovasc Diabetol. 2020;19:185.
  23. Khunti K, et al. Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nation- wide observational study in England. Lancet Diabetes Endocrinol. 2021;9:293–303.
  24. Drucker DJ. Diabetes, obesity, metabolism, and SARS- CoV-2 infection: the end of the beginning. Cell Metab. 2021;33:479–98.
  25. e risk factors for mortality of diabetic patients with severe COVID-19: a retrospective study of 167 severe COVID-19 cases in Wuhan. PLoS ONE. 2020;15:e0243602.
  26. Fleming N, Sacks LJ, Pham CT, Neoh SL, Ekinci EI. An over- view of COVID-19 in people with diabetes: pathophysiology and considerations in the inpatient setting. Diabet Med. 2021;38:e14509.
  27. Koh H, et al. Diabetes predicts severity of COVID-19 infection in a retrospective cohort: a mediatory role of the ammatory biomarker C-reactive protein. J Med Virol. 2021;93:3023–32.
  28. Peng X, et al. Promising therapy for heart failure in patients with severe COVID-19: calming the cytokine storm. Carer. 2021;35:231–47.
  29. Pitocco D, et al. Diabetes and severity of COVID-19: what is the link? Med Hypotheses. 2020;143:109923.
  30. Zheng M., et al. The cytokine profiles and immune response are increased in COVID-19 patients with type 2 diabetes mellitus. J Diabetes Res. 2021;2021:1–8.
  31. Roberts J, et al. Why Is COVID-19 more severe in patients e role of angiotensin-converting enzyme ammatory system. Front Cardiovasc Med. 2021;7:629933.
  32. Carrasco-Sánchez FJ, et al. Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19 regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry. Ann Med. 2021;53:103–16.
  33. Holman N, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study. Lancet Diabetes Endocrinol. 2020;8:823–33.
  34. Abdelhafiz A, Emmerton D, Sinclair A. Diabetes in COVID-19 pandemic-prevalence, patient characteristics and adverse outcomes. Int J Clin Pract. 2021. https://doi.org/10.1111/ ijcp.14112.
  35. Apicella M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020;8:782–92.
  36. Corcillo A, Whyte MB, Vas P, Karalliedde J. Microvascular disease in diabetes and severe COVID-19 outcomes. Lancet Diabetes Endocrinol. 2021;9:200–1.
  37. Petrilli CM, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966.
  38. Palaiodimos L, 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. Metabolism. 2020;108:154262.
  39. Scheen AJ. SGLT2 inhibition during the COVID-19 epidemic: friend or foe? Diabetes Metab. 2020;46:343–4.
  40. Shah H, Khan MSH, Dhurandhar NV, Hegde V. The triumvirate: why hypertension, obesity, and diabetes are risk factors for adverse effects in patients with COVID-19. Acta Diabetol. 2021;58:831–43.
  41. Shi Q, et al. Clinical characteristics and risk factors for mortality of COVID-19 patients with diabetes in Wuhan, China: a two-center retrospective study. Diabetes Care. 2020;43:1382–91.
  42. Sourij H, et al. COVID-19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission. Diabetes Obes Metab. 2021;23:589–98.
  43. Lasbleiz A, et al. Phenotypic characteristics and development of a hospitalization prediction risk score for outpatients with diabetes and COVID-19: the DIABCOVID study. J Clin Med. 2020;9:3726.
  44. Abe T, et al. Cardiovascular complications in COVID-19 patients with or without diabetes mellitus. Endocrinol Diabetes Metab. 2021;4:e00218.
  45. Lax SF, et al. Pulmonary arterial thrombosis in CO- VID-19 with fatal outcome : results from a prospective, single-center clinicopathologic case series. Ann Intern Med. 2020;173:350–61.
  46. Iba T, Connors JM, Nagaoka I, Levy JH. Recent advances in the research and management of sepsis-associated DIC. Int J Hematol. 2021;113:24–33.
  47. Shen Y, et al. Thresholds of glycemia and the outcomes of COVID-19 complicated with diabetes: a retrospective exploratory study using continuous glucose monitoring. Diabetes Care. 2021;44:976–82.
  48. Kapoor R, et al. Maintaining blood glucose levels in range (70–150 mg/ dL) is difficult in COVID-19 compared to non-COVID-19 ICU patients—a retrospective analysis. J Clin Med. 2020;9:3635.
  49. Pettrone K, et al. Characteristics and risk factors of hospitalized and nonhospitalized COVID-19 patients, Atlanta, Georgia, USA, March-April 2020. Emerg Infect Dis. 2021;27:1164–8.
  50. Smati S, et al. Relationship between obesity and severe COVID -19 outcomes in patients with type 2 diabetes: results from the CORONADO study. Diabetes Obes Metab. 2021;23:391–403.
  51. Sutter W, et al. Association of diabetes and outcomes in patients with COVID-19: propensity score-matched analyses from a French retrospective cohort. Diabetes Metab. 2021;47:101222.
  52. Gao F, et al. Obesity is a risk factor for greater COVID-19 severity. Diabetes Care. 2020;43:e72–4.
  53. Gao C, et al. Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. Eur Heart J. 2020;41:2058–66.
  54. Bikdeli B, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020;75:2950–73.
  55. Helms J, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensiv Care Med. 2020;46:1089–98.
  56. Harrison SL, Fazio-Eynullayeva E, Lane DA, Underhill P, Lip GYH. Higher mortality of ischaemic stroke patients hospitalized with COVID-19 compared to historical controls. Cerebrovasc Dis. 2021;50:326–31.
  57. Chioh FW, et al. Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation. Elife. 2021;10:e64909.
  58. Holland D, et al. Impact of the UK COVID-19 pandemic on HbA1c testing and its implications for diabetes diagnosis and management. Int J Clin Pract. 2021;75:e13980.
  59. Moreno R, et al. Impact of diabetes in patients waiting for invasive cardiac procedures during COVID-19 pandemic. Cardiovasc Diabetol. 2021;20:69.
  60. Jacob L, Rickwood S, Rathmann W, Kostev K. Change in glucose-lowering medication regimens in individuals with type 2 diabetes mellitus during the COVID-19 pandemic in Germany. Diabetes Obes Metab. 2021;23:910–5.
  61. Ledford CJW, et al. Quantifying worsened glycemic control during the COVID-19 pandemic. J Am Board Fam Med. 2021;34:S192–5.
  62. Klonoff DC, et al. Association between achieving inpatient glycemic control and clinical outcomes in hospitalized patients with COVID-19: a multicenter retrospective hospital- based analysis. Diabetes Care. 2021;44:578–85.
  63. Sardu C, et al. Outcomes in patients with hyperglycemia affected by COVID-19: can we do more on glycemic control? Diabetes Care. 2020;43:1408–15.
  64. Shen Y, Zhang L, Fan X, Zhou J. Glycemic fluctuations caused by COVID-19: Results from continuous glucose monitoring. Obes Med. 2021;22:100328.
  65. Chen L, et al. Association of early-phase in-hospital glycemic fluctuation with mortality in adult patients with Coronavirus disease 2019. Diabetes Care. 2021;44:865–73.
  66. Accili D. Can COVID-19 cause diabetes? Nat Metab. 2021;3:123–5.
  67. Misra S, et al. Comparison of diabetic ketoacidosis in adults during the SARS-CoV-2 outbreak and over the same time period for the preceding 3 years. Diabetes Care. 2021;44:e29–31.
  68. Kempegowda P, et al. Effect of COVID-19 on the clinical course of diabetic ketoacidosis (DKA) in people with type 1 and type 2 diabetes. Endocr Connect. 2021;10:371–7.
  69. Braithwaite SS, Bavda DB, Idrees T, Qureshi F, Soetan OT. Hypoglycemia reduction strategies in the ICU. Curr Diabetes Rep. 2017;17:133.
  70. Bhatt AS, et al. Fewer hospitalizations for acute cardiovascular conditions during the COVID-19 pandemic. J Am Coll Cardiol. 2020;76:280–8.
  71. De Filippo O, et al. Reduced rate of hospital admissions for ACS during Covid-19 outbreak in Northern Italy. N Engl J Med. 2020;383:88–9.
  72. De Rosa S, et al. Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era. Eur Heart J. 2020;41:2083–8.
  73. De Luca G, et al. Impact of COVID-19 pandemic and dia- betes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry. Cardiovasc Diabetol. 2020;19:215.
  74. D’Amario D, Rodolico D, Cappannoli L, Migliaro S, Crea F. Are we missing something in the management of acute coronary syndromes in COVID- 9-negative patients? J Am Coll Cardiol. 2020;76:2573–4.
  75. Einstein AJ, et al. International impact of COVID-19 on the diagnosis of heart disease. J Am Coll Cardiol. 2021;77:173–85. 76. Banerjee A, et al. Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic. Eur J Prev Cardiol. 2021. https://doiorg/10.1093/eurjpc/zwaa155.
  76. Singh AK, Singh R, Saboo B, Misra A. Non-insulin anti- diabetic agents in patients with type 2 diabetes and COVID-19: a critical appraisal of literature. Diabetes Metab Syndr. 2021;15:159–67.
  77. Schofield J, Leelarathna L, Thabit H. COVID-19: impact of and on diabetes. Diabetes Ther. 2020;11:1429–35
  78.  
  79. Bramante CT, et al. Metformin and risk of mortality in pa- tients hospitalised with COVID-19: a retrospective cohort analysis. Lancet Healthy Longev. 2021;2:e34–41.
  80. Crouse AB, et al. Metformin use is associated with reduced mortality in a diverse population with COVID-19 and dia- betes. Front Endocrinol. 2021;11:600439.
  81. Dardano A, Del Prato S. Metformin: an inexpensive and effective treatment in people with diabetes and COVID-19? Lancet Healthy Longev. 2021;2:e6–7.
  82. Lalau J-D, et al. Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19. Diabetes Metab. 2021;47:101216.
  83. Pal R, et al. Dipeptidyl peptidase-4 inhibitor use and mortal- ity in COVID-19 patients with diabetes mellitus: an updated systematic review and meta-analysis. Ther Adv Endocrinol Metab. 2021;12:2042018821996482.
  84. Ursini F, Ciaffi J, Landini MP, Meliconi R. COVID-19 and diabetes: is metformin a friend or foe? Diabetes Res Clin Pract. 2020;164:108167.
  85. Wang J, et al. Association of metformin with susceptibility to COVID-19 in people with Type 2 diabetes. J Clin Endocrinol Metab. 2021;106:1255–68.
  86. Lui DTW, Tan KCB. Is metformin a miracle or a men- ace in COVID-19 patients with type 2 diabetes? J Diabetes Investig. 2021;12:479–81.
  87. Lally MA, et al. Metformin is associated with decreased 30- day mortality among nursing home residents infected with SARS-CoV2. J Am Med Dir Assoc. 2021;22:193–8.
  88. Kahkoska AR, et al. Association between glucagon-like pep- tide 1 receptor agonist and sodium-glucose Cotransporter 2 inhibitor use and COVID-19 outcomes. Diabetes Care. 2021;44:1564–72.
  89. Bonora BM, Avogaro A, Fadini GP. Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: narrative review and meta-analysis. J Endocrinol Invest. 2021;44:1379–86.
  90. Fadini GP, et al. Exposure to dipeptidyl-peptidase-4 inhibitors and COVID -19 among people with type 2 diabetes: a case-control study. Diabetes Obes Metab. 2020;22:1946–50.
  91. Iacobellis G. COVID-19 and diabetes: Can DPP4 inhibition play a role? Diabetes Res Clin Pract. 2020;162:108125.
  92. Kow CS, Hasan SS. Use of DPP-4 inhibitors in patients with
    COVID-19. Acta Diabetol. 2021;58:245–6.
  93. Nauck MA, Meier JJ. Reduced COVID-19 mortality with
    sitagliptin treatment? Weighing the dissemination of potentially lifesaving findings against the assurance of high scientific standards. Diabetes Care. 2020;43:2906–9.
  94. Noh Y, et al. Association between DPP-4 inhibitors and COVID-19 related outcomes among patients with type 2 diabetes. Diabetes Care. 2021;44:e64–6.
  95. Israelsen SB, et al. Comparable COVID-19 outcomes with current use of GLP-1 receptor agonists, DPP-4 inhibitors or SGLT-2 inhibitors among patients with diabetes who tested positive for SARS-CoV-2. Diabetes Obes Metab. 2021;23:1397–401.
  96. Roussel R, et al. Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID -19 in hospitalized patients with type 2 diabetes: a propensity score analysis from the CORONADO study. Diabetes Obes Metab. 2021;23:1162–72.
  97. Scheen AJ. DPP-4 inhibition and COVID-19: From initial concerns to recent expectations. Diabetes Metab. 2021;47:101213.
  98. Solerte SB, et al. Sitagliptin treatment at the time of hospitalization was associated with reduced mortality in patients with type 2 diabetes and COVID-19: a multicenter, casecontrol, retrospective observational study. Diabetes Care. 2020;43:2999–3006.
  99. Valencia I, et al. DPP4 and ACE2 in diabetes and COVID-19: therapeutic targets for cardiovascular complications? Front Pharmacol. 2020;11:1161.
  100. Ramos-Rincón JM, et al. Cardiometabolic Therapy and mortality in very old patients with diabetes hospitalized due to COVID-19. J Gerontol Ser A. 2021;76:e102–9.
  101. Schernthaner G. Effects of a DPP-4 inhibitor and RAS blockade on clinical outcomes of patients with diabetes and COVID-19 (Diabetes Metab J 2021;45:251–9). Diabetes Metab J. 2021;45:615–6.
  102. Donath MY. Glucose or insulin, which is the culprit in patients with COVID-19 and diabetes? Cell Metab. 2021;33:2–4.
  103. Falcetta P, et al. Impact of COVID-19 lockdown on glucose control of elderly people with type 2 diabetes in Italy. Diabetes Res Clin Pract. 2021;174:108750.
  104. Yu B, Li C, Sun Y, Wang DW. Insulin treatment is associated with increased mortality in patients with COVID-19 and type 2 diabetes. Cell Metab. 2021;33:65-77.e2.
  105. Schernthaner G. Can glucose-lowering drugs affect the prognosis of COVID-19 in patients with type 2 diabetes? Lancet Diabetes Endocrinol. 2021;9:251–2.
  106. Kosiborod MN, et al. Dapagliflozin in patients with cardio- metabolic risk factors hospitalised with COVID-19 (DARE- 19): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2021;9:586–94.
  107. Giugliano D, et al. Feasibility of simplification from a basal- bolus insulin regimen to a fixed-ratio formulation of basal insulin plus a GLP-1RA or to basal insulin plus an SGLT2 inhibitor: BEYOND, a randomized pragmatic trial. Diabetes Care. 2021;44:1353–60.
  108. Batista DV, de Almeida Vieira CAF, Costa TA, Lima EG. COVID-19-associated euglycemic diabetic ketoacidosis in a patient with type 2 diabetes on SGLT2 inhibitor: a case report. Diabetol Int. 2021;12:313–6.
  109. Dass B, Beck A, Holmes C, Morton G. Euglycemic DKA (euDKA) as a presentation of COVID-19. Clin Case Rep. 2021;9:395–8.
  110. Fang J, Genco M, Caskey RN. COVID-19 precipitating euglycaemic diabetic ketoacidosis with SGLT2 inhibitor use. Eur J Case Rep Intern Med. 2020;7:001943.
  111. Gorthi RS, Kamel G, Dhindsa S, Nayak RP. COVID-19 presenting with diabetic ketoacidosis: a case series. AACE Clin Case Rep. 2021;7:6–9.
  112. Morrison N, Barnett K, Tantum J, Morrison HK, Wha- len M. A case of euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus and COVID-19. Cureus. 2020;12:e12029.
  113. Ozer O, Yorulmaz G. Euglycemic diabetic ketoacidosis associated with empagliflozin use in the course of the SARS- Cov-2 pandemic. J Coll Physicians Surg Pak. 2020;30:110–1.
  114. Pasquel FJ, et al. Characteristics of and mortality associ- ated with diabetic ketoacidosis among US patients hospitalized with or without COVID-19. JAMA Netw Open. 2021;4:e211091.
  115. Vitale RJ, Valtis YK, McDonnell ME, Palermo NE, Fisher NDL. Euglycemic diabetic ketoacidosis with COVID-19 infection in patients with type 2 diabetes taking SGLT2 inhibitors. AACE Clin Case Rep. 2021;7:10–3.
  116. Xu C, Zia U. Recovery from acute kidney injury with diabetic ketoacidosis following SARS-CoV-2 infection: a case report and literature review. Cureus. 2020;12:e11702.
  117. Kosiborod M, et al. Effects of dapagliflozin on prevention of major clinical events and recovery in patients with respiratory failure because of COVID-19: design and rationale for the DARE-19 study. Diabetes Obes Metab. 2021;23:886–96.
  118. Ayoubkhani D, et al. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ. 2021;372:n693.
  119. Pintaudi B, et al. Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study. Cardiovasc Diabetol. 2021;20:59.
  120. Nargesi AA, et al. Contemporary national patterns of eligibility and use of novel cardioprotective antihyperglycemic agents in type 2 diabetes mellitus. J Am Heart Assoc. 2021;10:e021084.
  121. For the SEMI-COVID-19 Network, et al. Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose- lowering drugs: a nationwide cohort study. BMC Med. 2020;18:359.
  122. Sainsbury C, et al. Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: a populationbased retrospective cohort study. Diabetes Obes Metab. 2021;23:263–9.
  123. Kow CS, Hasan SS. Mortality risk with preadmission metformin use in patients with COVID-19 and diabetes: a meta-analysis. J Med Virol. 2021;93:695–7.

https://doi.org/10.1186/s12933-021-01389-1

 

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