Doms № 5 -2022

Ведення пацієнтів з цукровим діабетом 2-го типу до, під час та після зараження Covid-19: які докази існують?

 

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

Лешек Чуприняк, Дрор Дікер, Роджер Леманн, Мартін Празні, Гунтрам Шернтанер

 

Резюме

Захворюваність пацієнтів інфекцією Covid-19 ставить лікарів перед новими проблемами лікування цукрового діабету 2-го типу, включно з питанням про те, чи слід коригувати глюкозознижуючу терапію під час захворювання та як повертатись до нормального лікування після усунення симптомів Covid-19. У зв’язку з раптовим початком пандемії лікарі були змушені приймати важливі клінічні рішення за выдсутності найдійних доказів або послідовних рекомендацій. Ризик для пацієнтів посилюється поширеністю серцево-судинних захворювань у цій популяції, які разом з цукровим діабетом є основним фактором ризику тяжкого перебігу і смерті від Covid-19. Ми зібрались як експерти з регіону Центральної та Східної Європи, щоб сформулювати поради, які ми можемо надати в контексті цукрового діабету 2-го типу та Covid-19, враховуючи дані, отримані у пацієнтів до, під час та після зараження. Ми розглянули рекомендації, які були опубліковані на сьогоднішній день, і оцінили доступні, але наразі обме- жені дані великих спостережних досліджень та рандомізованого контрольного дослідження DARE-19. Слід зазначити, що ми виявили відсутність рекомендацій щодо оптимальної цукрознижуючої терапії після одужання від Covid-19, і припустили, що це може дати можливість оптимізувати лікування та протидіяти клінічній інерції, яка передувала пандемії. Крім того, ми наголошуємо, що оптимізація стосується не лише контролю глікемії, а й інших факторів, таких як серцево-нирковий захист. Хоча ми з нетерпінням чекаємо на появу нових доказів, які, як ми сподіваємось, дозволять усунути ці прогалини, виходячи з нашого сукупного клінічного досвіду, ми одночасно описуємо можливі підходи до керування глюкозознижуючою терапією в ситуації, коли пацієнти з Covid-19 одужують і повертаються до свого стандартного лікування.

Ключові слова: Covid-19, цукровий діабет 2-го типу, глюкозознижуюча терапія

Література:

  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.