Glycemia control and choice of antihyperglycemic therapy in patients with type 2 diabetes mellitus and COVID-19: a consensus decision of the board of experts of the Russian association of endocrinologists

A dangerous viral disease COVID-19, caused by a new RNA coronavirus SARS-COV-2, has been actively spreading in the world since December 2019. The main manifestations of this disease are bilateral pneumonia, often accompanied by the development of acute respiratory syndrome and respiratory failure. Patients with diabetes mellitus (DM) are at high risk of infection with the SARS-COV-2 virus, severe illness and death.

Maintaining of target glycemic levels is the most important factor in a favorable outcome of COVID-19 in both type 1 and type 2 DM. The choice of antihyperglycemic therapy in a patient with DM in the acute period of COVID-19 depends on the initial therapy, the severity of hyperglycemia, the severity of the viral infection and the patient’s clinical condition.

The article presents the recommendations of the board of experts of the Russian Association of Endocrinologists on glycemic control and the choice of antihyperglycemic therapy in patients with type 2 DM and COVID-19, and also on the use of glucocorticosteroids used in the treatment of COVID-19 in patients with type 2 DM.

1. Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2020;8(1):e35. doi: https://doi.org/10.22037/aaem.v8i1.600

2. Richardson S, Hirsch JS, Narasimhan M, 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. doi: https://doi.org/10.1001/jama.2020.6775

3. Rawshani A, Kjölhede EA, Rawshani A, et al. Severe COVID-19 in people with type 1 and type 2 diabetes in Sweden: A nationwide retrospective cohort study. Lancet Reg Heal - Eur. 2021;4(10):100105. doi: https://doi.org/10.1016/j.lanepe.2021.100105

4. Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 2020;8(10):813-822. doi: https://doi.org/10.1016/S2213-8587(20)30272-2

5. Holman N, Knighton P, Kar P, 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(10):823-833. doi: https://doi.org/10.1016/S2213-8587(20)30271-0

6. Ando W, Horii T, Uematsu T, et al. Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States. Sci Rep. 2021;11(1):17968. doi: https://doi.org/10.1038/s41598-021-96720-x

7. Bode B, Garrett V, Messler J, et al. Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States. J Diabetes Sci Technol. 2020;14(4):813-821. doi: https://doi.org/10.1177/1932296820924469

8. Pettus J, Skolnik N. Importance of diabetes management during the COVID-19 pandemic. Postgrad Med. 2021;133(8):912-919. doi: https://doi.org/10.1080/00325481.2021.1978704

9. Wang S, Ma P, Zhang S, et al. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study. Diabetologia. 2020;63(10):2102-2111. doi: https://doi.org/10.1007/s00125-020-05209-1

10. Zhu L, She Z-G, Cheng X, 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):1068-1077.e3. doi: https://doi.org/10.1016/j.cmet.2020.04.021

11. Vremennye metodicheskie rekomendatsii «Profilaktika, diagnostika i lechenie novoi koronavirusnoi infektsii (COVID-19)». Versiya 14. 27.12.2021. (In Russ.).

12. Antsiferov MB, Andreeva AV, Markova TN. Metodicheskie rekomendatsii «Organizatsiya spetsializirovannoi meditsinskoi pomoshchi vzroslomu naseleniyu s sakharnym diabetom v usloviyakh novoi koronavirusnoi infektsii COVID-19»; 2020. (In Russ.).

13. Czupryniak L, Dicker D, Lehmann R, et al. The management of type 2 diabetes before, during and after Covid-19 infection: what is the evidence? Cardiovasc Diabetol. 2021;20(1):198. doi: https://doi.org/10.1186/s12933-021-01389-1

14. Hasan SS, Kow CS, Bain A, et al. Pharmacotherapeutic considerations for the management of diabetes mellitus among hospitalized COVID-19 patients. Expert Opin Pharmacother. 2021;22(2):229-240. doi: https://doi.org/10.1080/14656566.2020.1837114

15. Gupta Y, Goyal A, Kubihal S, et al. A guidance on diagnosis and management of hyperglycemia at COVID care facilities in India. Diabetes Metab Syndr. 2021;15(1):407-413. doi: https://doi.org/10.1016/j.dsx.2021.01.015

16. Concise advice on inpatient diabetes (COVID:Diabetes): Hyperglycaemia/diabetes Guidance For People With COVID-19 Infections Managed In A Virtual Ward: A Guide For Healthcare Professionals - abcd.care. [Accessed January 21, 2022]. Available from: https://abcd.care/sites/abcd.care/files/site_uploads/Resources/COVID-19/COvID_Virtual_Ward_v1.2.pdf

17. Algoritmy spetsializirovannoi meditsinskoi pomoshchi bol’nym sakharnym diabetom (10-i vypusk, dopolnennii). Ed by Dedov II, Shestakova MV, Mayorova AYu. Moscow: 2022. (In Russ.). doi: https://doi.org/10.14341/DM12802

18. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693-704. doi: https://doi.org/10.1056/NEJMoa2021436

19. Aberer F, Hochfellner DA, Sourij H, Mader JK. A Practical Guide for the Management of Steroid Induced Hyperglycaemia in the Hospital. J Clin Med. 2021;10(10):2154. doi: https://doi.org/10.3390/jcm10102154

20. Noreen S, Maqbool I, Madni A. Dexamethasone: Therapeutic potential, risks, and future projection during COVID-19 pandemic. Eur J Pharmacol. 2021;894:173854. doi: https://doi.org/10.1016/j.ejphar.2021.173854

21. Rayman G, Lumb AN, Kennon B, et al. Dexamethasone therapy in COVID-19 patients: implications and guidance for the management of blood glucose in people with and without diabetes. Diabetes Metab. 2021;38(1):e14378. doi: https://doi.org/10.1111/dme.14378

22. Stewart R. Dexamethasone therapy in COVID-19 patients: implications and guidance for the management of blood glucose in people with and without diabetes. Diabetes Metab. 2021;38(1):e14378. doi: https://doi.org/10.1111/dme.14378

23. Scheen AJ. Metformin and COVID-19: From cellular mechanisms to reduced mortality. Diabetes Metab. 2020;46(6):423-426. doi: https://doi.org/10.1016/j.diabet.2020.07.006

24. Sharma S, Ray A, Sadasivam B. Metformin in COVID-19: A possible role beyond diabetes. Diabetes Res Clin Pract. 2020;164:108183. doi: https://doi.org/10.1016/j.diabres.2020.108183

25. Wu J, Zhang J, Sun X, et al. Influence of diabetes mellitus on the severity and fatality of SARS‐CoV‐2 (COVID‐19) infection. Diabetes, Obes Metab. 2020;22(10):1907-1914. doi: https://doi.org/10.1111/dom.14105

26. Erdmann E, Wilcox R. Pioglitazone and mechanisms of CV protection. QJM. 2010;103(4):213-228. doi: https://doi.org/10.1093/qjmed/hcp168

27. 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(7):1379-1386. doi: https://doi.org/10.1007/s40618-021-01515-6

28. Drucker DJ. Coronavirus Infections and Type 2 Diabetes—Shared Pathways with Therapeutic Implications. Endocr Rev. 2020;41(3):1379-1386. doi: https://doi.org/10.1210/endrev/bnaa011

29. Krejner-Bienias A, Grzela K, Grzela T. DPP4 Inhibitors and COVID-19–Holy Grail or Another Dead End? Arch Immunol Ther Exp (Warsz). 2021;69(1):1. doi: https://doi.org/10.1007/s00005-020-00602-5

30. Lu G, Hu Y, Wang Q, et al. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature. 2013;500(7461):227-231. doi: https://doi.org/10.1038/nature12328

31. Sazgarnejad S, Yazdanpanah N, Rezaei N. Anti-inflammatory effects of GLP-1 in patients with COVID-19. Expert Rev Anti Infect Ther. 2021;500(7461):1-9. doi: https://doi.org/10.1080/14787210.2021.1964955

32. Kosiborod M, Berwanger O, Koch GG, 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;23:886-896. doi: https://doi.org/10.1111/dom.14296

33. Garvey WT, Van Gaal L, Leiter LA, et al. Effects of canagliflozin versus glimepiride on adipokines and inflammatory biomarkers in type 2 diabetes. Metabolism. 2018;85:32-37. doi: https://doi.org/10.1016/j.metabol.2018.02.002

34. Couselo-Seijas M, Agra-Bermejo RM, Fernández AL, et al. High released lactate by epicardial fat from coronary artery disease patients is reduced by dapagliflozin treatment. Atherosclerosis. 2020;292:60-69. doi: https://doi.org/10.1016/j.atherosclerosis.2019.11.016

35. Kan C, Zhang Y, Han F, et al. Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2021;12. doi: https://doi.org/10.3389/fendo.2021.708494

36. Avogaro A, Bonora B, Fadini GP. Acta Managing diabetes in diabetic patients with COVID: where do we start from? Diabetologica. 2021;58:1441-1450. doi: https://doi.org/10.1007/s00592-021-01739-1$

37. Ramos-Rincón JM, Pérez-Belmonte LM, Carrasco-Sánchez FJ, et al. Cardiometabolic Therapy and Mortality in Very Old Patients With Diabetes Hospitalized due to COVID-19. Lipsitz L, ed. Journals Gerontol Ser A. 2021;76(8):e102-e109. doi: https://doi.org/10.1093/gerona/glab124

38. Cariou B, Hadjadj S, Wargny M, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia. 2020;63(8):1500-1515. doi: https://doi.org/10.1007/s00125-020-05180-x

39. Silverii GA, Monami M, Cernigliaro A, et al. Are diabetes and its medications risk factors for the development of COVID-19? Data from a population-based study in Sicily. Nutr Metab Cardiovasc Dis. 2021;31(2):396-398. doi: https://doi.org/10.1016/j.numecd.2020.09.028

40. Khunti K, Knighton P, Zaccardi F, et al. Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England. Lancet Diabetes Endocrinol. 2021;9(5):293-303. doi: https://doi.org/10.1016/S2213-8587(21)00050-4

41. Izzi-Engbeaya C, Distaso W, Amin A, 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(1):e001858. doi: https://doi.org/10.1136/bmjdrc-2020-001858

42. Lukito AA, Pranata R, Henrina J, et al. The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis. Diabetes Metab Syndr. 2020;14(6):2177-2183. doi: https://doi.org/10.1016/j.dsx.2020.11.006

43. 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(2):695-697. doi: https://doi.org/10.1002/jmv.26498

44. Li Y, Yang X, Yan P, et al. Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis. Front Med. 2021;8. doi: https://doi.org/10.3389/fmed.2021.704666

45. 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: https://doi.org/10.1016/j.obmed.2020.100290

46. Yang W, Sun X, Zhang J, et al. The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus. Diabetes Res Clin Pract. 2021;178:108977. doi: https://doi.org/10.1016/j.diabres.2021.108977

47. Nyland JE, Raja-Khan NT, Bettermann K, et al. Diabetes, Drug Treatment and Mortality in COVID-19: A Multinational Retrospective Cohort Study. SSRN Electron J. 2020. doi: https://doi.org/10.2139/ssrn.3725612

48. Solerte SB, D’Addio F, Trevisan R, 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, Case-Control, Retrospective, Observational Study. Diabetes Care. 2020;43(12):2999-3006. doi: https://doi.org/10.2337/dc20-1521

49. Mirani M, Favacchio G, Carrone F, et al. Impact of Comorbidities and Glycemia at Admission and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes With COVID-19: A Case Series From an Academic Hospital in Lombardy, Italy. Diabetes Care. 2020;43(12):3042-3049. doi: https://doi.org/10.2337/dc20-1340

50. Wargny M, Potier L, Gourdy P, et al. Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study. Diabetologia. 2021;64(4):778-794. doi: https://doi.org/10.1007/s00125-020-05351-w

51. Noh Y, Oh I-S, Jeong HE, et al. Association Between DPP-4 Inhibitors and COVID-19–Related Outcomes Among Patients With Type 2 Diabetes. Diabetes Care. 2021;44(4):e64-e66. doi: https://doi.org/10.2337/dc20-1824

52. Fadini GP, Morieri ML, Longato E, 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(10):1946-1950. doi: https://doi.org/10.1111/dom.14097

53. Strollo R, Maddaloni E, Dauriz M, et al. Use of DPP4 inhibitors in Italy does not correlate with diabetes prevalence among COVID-19 deaths. Diabetes Res Clin Pract. 2021;171(5):108444. doi: https://doi.org/10.1016/j.diabres.2020.108444

54. Roussel R, Darmon P, Pichelin M, 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(5):1162-1172. doi: https://doi.org/10.1111/dom.14324

55. Zhou J-H, Wu B, Wang W-X, et al. No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19. World J Clin Cases. 2020;8(22):5576-5588. doi: https://doi.org/10.12998/wjcc.v8.i22.5576

56. Israelsen SB, Pottegård A, Sandholdt H, 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(6):1397-1401. doi: https://doi.org/10.1111/dom.14329

57. Kahkoska AR, Abrahamsen TJ, Alexander GC, et al. Association Between Glucagon-Like Peptide 1 Receptor Agonist and Sodium–Glucose Cotransporter 2 Inhibitor Use and COVID-19 Outcomes. Diabetes Care. 2021;44(7):1564-1572. doi: https://doi.org/10.2337/dc21-0065

58. Kosiborod MN, Esterline R, Furtado RHM, et al. Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2021;9(9):586-594. doi: https://doi.org/10.1016/S2213-8587(21)00180-7