Hypoglycemic Therapy and the Course of Post-Covid Syndrome, is There a Connection?

Diabetes mellitus (both type 1 and type 2) is considered one of the risk factors for severe COVID-19 and death from this infection. Past infection with COVID-19 leads to deterioration in the control of existing diabetes mellitus, progression of pre-diabetes to diabetes, an increase in the number of new cases of diabetes and an increase in the proportion of glucocorticoid-induced diabetes, which significantly aggravates the course of post-COVID syndrome for this category of patients. Antihyperglycemic drugs may influence the pathogenesis of COVID-19, which may be of relevance for the treatment of patients with type 2 diabetes mellitus and post-COVID syndrome. The review also presents our own data on the effect of various regimens of oral hypoglycemic agents on post-COVID syndrome in people with type 2 diabetes mellitus. The observation showed that the use of dipeptidyl peptidase-4 inhibitors as part of a treatment strategy in patients with type 2 diabetes mellitus with a past COVID-19 infection was associated with a decrease in the duration and severity of post-COVID symptoms.

1. Steenblock Ch., Schwarz P.E. H., Ludwig B. et al. COVID-19 and metabolic disease: mechanisms and clinical management. Lancet Diabetes Endocrinol. 2021; 9 (11): 786-798. https://doi.org/10.1016/S2213-8587(21)00244-8

2. Ignatenko G.A., Bagrij A.Je., Oprishhenko A.A. et al. Diabetes mellitus: a guide for physicians. Donetsk, RB Pozitiv. 2022; 640 р.

3. Apicella M., Campopiano M.C., Mazoni L. et al. COVID-19 in people with diabetes: understanding the reasons for worse out-comes. Lancet Diabetes Endocrinol. 2020; 8 (9): 782-792. doi: 10.1016/S2213-8587(20)30238-2

4. Lim S., Bae J.H., Kwon H.S. et al. COVID-19 and diabetes mellitus: From pathophysiology to clinical management. Nat Rev Endocrinol. 2021; 17 (1): 11-30. https://doi.org/10.1038/s41574-020-00435-4

5. Davis H.E., Assaf G.S., McCorkell L. et al. Characterizing long COVID in an international: 7 months of symptoms and their impact. EClini-calMedicine. 2021; 38: 101019. https://doi.org/10.1016/j.eclinm.2021.101019

6. Nalbandian A., Sehgal K., Gupta A. et al. Post-acute COVID-19 syndrome. Nature Medicine. 2021; 27 (4): 601-615. doi: 10.1038/s41591-021-01283-z

7. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [May 31, 2022]

8. Kosiborod M.N., Esterline R., Furtado R.H. M. 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: 10.1016/S2213-8587(21)00180-7

9. Manu P. Drug Therapy for Unexplained Dyspnea in Post-COVID-19 Fatigue Syndrome: Empagliflozin and Sildenafil. Am J Ther. 2022; 29 (4): e447-e448. doi: 10.1097/MJT.0000000000001483. PMID: 35412483

10. Kang Y., Zhan F., He M. et al. Anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis. Vascul Pharmacol. 2020; 133-134: 106779. doi: 10.1016/j.vph.2020.106779

11. Pawlos A., Broncel M., Wozniak E. et al. Neuroprotective effect of SGLT2 inhibitors. Molecules. 2021; 26: 7213. doi: 10.3390/molecules26237213

12. Wiciński M., Wódkiewicz E., Górski K. et al. Perspective of SGLT2 inhibition in treatment of conditions connected to neuronal loss: focus on alzheimer’s disease and ischemia-related brain injury. Pharmaceuticals (Basel). 2020; 13: 379. doi: 10.3390/ph13110379

13. Bornstein S.R., Rubino F., Khunti K. et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020; 8 (6): 546-550. doi: 10.1016/S2213-8587(20)30152-2

14. K.V. Zhmerenetskii, A.V. Vitko, T.A. Petrichko et al. Difficult issues in the management of patients with COVID-19 comorbid for cardiovascular disease and type 2 diabetes mellitus. Far Eastern Medical Journal. 2020; 2: 102-114. http://dx.doi.org/10.35177/1994-5191-2020-2-101-113

15. Kleine-Weber H., Schroeder S., Krüger N. et al. Polymorphisms in dipeptidylpeptidase 4 reduce host cell entry of Middle East respiratory syndrome coronavirus. Emerg. Microbes Infect. 2020; 9 (1): 155-168. doi: 10.1080/22221751.2020.1713705

16. Solerte S.B., 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. https://doi.org/10.2337/dc20-1521

17. Mirani M., Favacchio G., Carrone F. et al. Impact of comorbidities, glycemia at admission, and DPP-4 inhibitors in type 2 diabetic patients with COVID-19: a case series from an academic hospital in Lombardy, Italy. Diabetes Care. 2020; 43 (12): 3042-3049. https://doi.org/10.2337/dc20-1340

18. Dalan R., Ang L.W., Tan W.Y. T. et al. The association of hypertension and diabetes pharmacotherapy with COVID-19 severity and immune signatures: an observational study. Eur. Heart J. Cardiovasc. Pharmacother. 2021; 7 (3): e48-e51. https://doi.org/10.1093/ehjcvp/pvaa098

19. Scherer P.E., Kirwan J.P., Rosen C.J. Post-acute sequelae of COVID-19: A metabolic perspective. Elife. 2022; 11: e78200. doi: 10.7554/eLife.78200