GLP-1 receptor agonists in the management of COVID-19 and long COVID for patients with underlying metabolic disorders
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HINCHLIFFE, Nigel W et al.
GLP-1 receptor agonists in the management of COVID-19 and long COVID for patients with underlying metabolic disorders.
Medical Research Archives, [S.l.], v. 13, n. 4, apr. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6406>. Date accessed: 15 may 2025.
doi: https://doi.org/10.18103/mra.v13i4.6406.
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The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Huang Y, Lu Y, Huang YM Wang M, Ling W, Sui Y, Zhao HL. Obesity in patients with COVID-19: a systematic review and meta-analysis. Metabolism. 2020; 113:154378. doi:10.1016/j.metabol.2020.15 4378.
2. Yin Y, Rohli KE, Shen P, Lu H, Liu Y, Dou Q, Zhang L, Kong X, Yang S, Jia P. The epidemiology, pathophysiological mechanisms, and management toward COVID-19 patients with type 2 diabetes: a systematic review. Prim Care Diabetes. 2021; 15(6): 899-909.
3. Scirica BM, Lincoff AM, Lingvay I, Bogdanski P, Buscemi S, Colhoun H, Craciun AE, Ezhov M, Hardt-Lindberg S, Kleist Jeppesen O, Matos ALSA, Node K, Schiele F, Toplak H, van Beek A, Weeke PE, Wiviott SD, Deanfield J, Ryan D. The effect of semaglutide on mortality and COVID-19-related deaths: an analysis from the SELECT Trial. J Am Coll Cardiol. 2024; 84(17):1632-1642. doi: 10.1016/j.jac c.2024.08.007.
4. Campbell JE & Drucker DJ. Pharmacology physiology and mechanisms of incretin hormone action. Cell Metab. 2013; 17(6):819-837. doi: 10.101 6/j.cmet.2013.04.008.
5. Hammoud R & Drucker DJ. Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. Nat. Rev. Endocrinol. 2023; 19:201–216. doi: 10.1038/s41574-022-00783-3.
6. Hariyanto TI, Intan D, Hananto JE, Putri C, Kurniawan A. Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression. Diabetes Research and Clinical Practice. 2021; 179:109031. doi: 10.1016/j.diabres.2021.109031.
7. Wander PL, Lowy E, Beste LA, Tulloch-Palomino L, Korpak A, Peterson AC, Kahn SE, Boyko EJ. Prior glucose-lowering medication use and 30-day outcomes among 64,892 veterans with diabetes and COVID-19. Diabetes Care. 2021; 44(12):2708-2713.
8. Chen Y, Lv X, Lin S, Arshad M and Dai M. The association between antidiabetic agents and clinical outcomes of COVID-19 patients with diabetes: a Bayesian Network meta-analysis. Front. Endocrinol. 2022; 13:895458. doi: 10.3389/fendo.2022.895458.
9. Sudhakar M, Winfred SB, Meiyazhagan G, Venkatachalam DP. Mechanisms contributing to adverse outcomes of COVID-19 in obesity. Mol Cell Biochem. 2022; 477:1155–1193.
10. Rey-Reñones C, Martinez-Torres S, Martín-Luján FM, Pericas C, Redondo A, Vilaplana-Carnerero C, Dominguez A, Grau M. Type 2 diabetes mellitus and COVID-19: a narrative review. Biomedicines. 2022; 10(9):2089.
doi: 10.3390/biomedicines10092089.
11. Abudalo RA, Alqudah AM, Roarty C, Athamneh RY, Grieve DJ. Oxidative stress and inflammation in COVID-19: potential application of GLP-1 receptor agonists. Eur Rev Med Pharmacol Sci. 2023; 27(13): 6459-6471. doi: 10.26355/eurrev_202307_33007.
12. Mehdi SF, Pusapati S, Anwar MS, Lohana D, Kumar P, Nandula SA, Nawaz FK, Tracey K, Yang H, LeRoith D, Brownstein MJ and Roth J. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front. Immunol. 2023; 14:1148209. doi: 10.3389/fim mu.2023.1148209.
13. Wang S, Ma P, Zhang S, Song S, Wang Z, Ma Y, Xu J, Wu F, Duan L, Yin Z, Luo H, Xiong N, Xu M, Zeng T, Jin Y. 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: 10.1007/s 00125-020-05209-1.
14. Holman N, Knighton P, Kar P, O'Keefe J, Curley M, Weaver A, Barron E, Bakhai C, Khunti K, Wareham NJ, Sattar N, Young B, Valabhji J. 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: 10.1016/S2213-8587(20) 30271-0.
15. Aroda VR. A review of GLP-1 receptor agonists: Evolution and advancement, through the lens of randomised controlled trials. Diabetes Obes Metab. 2018; 20 (Suppl 1):22-33. doi:10.1111/dom.13162.
16. Graña C, Ghosn L, Evrenoglou T et al. Efficacy and safety of COVID-19 vaccines. Cochrane Database Syst Rev. 2022; 12(12):CD015477. doi: 10.1002/146 51858.CD015477.
17. Greenhalgh T, Sivan M, Perlowski A, Nikolich JŽ. Long COVID: a clinical update. Lancet. 2024; 404(10453):707-724.
18. PHOSP-COVID Collaborative Group. Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. Lancet Respir Med. 2022; 10 (8):761-775. doi: 10.1016/S2213-2600(22)00127-8.
19. Su Y, Yuan D, Chen DG, Ng RH et al. (ISB-Swedish COVID-19 Biobanking Unit). Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022; 185(5):881-895.e20. doi: 10.1016/j.cell.2022.01.014.
20. Barrett CE, Koyama AK, Alvarez P, Chow W, Lundeen EA, Perrine CG, Pavkov ME, Rolka DB, Wiltz JL, Bull-Otterson L, Gray S, Boehmer TK, Gundlapalli AV, Siegel DA, Kompaniyets L, Goodman AB, Mahon BE, Tauxe RV, Remley K, Saydah S. Risk for newly diagnosed diabetes >30 days after SARS-CoV-2 infection among persons aged <18 Years - United States, March 1, 2020-June 28, 2021. MMWR Morb Mortal Wkly Rep. 2022; 71(2):59-65. doi: 10.15585/mmwr.mm7102e2.
21. Montefusco L, Ben Nasr M, D'Addio F, Loretelli C, Rossi A, Pastore I, Daniele G, Abdelsalam A, Maestroni A, Dell'Acqua M et al. Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection. Nat Metab. 2021; 3(6):774-785. doi: 10.1038/s42255-021-004 07-6.
22. Xie Y, Al-Aly Z Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2022; 10(5):311-321. doi: 10.101 6/S2213-8587(22)00044-4.
23. Tandon P, Abrams ND, Avula LR, Carrick DM, Chander P, Divi RL, Dwyer JT, Gannot G, Gordiyenko N, Liu Q, Moon K, PrabhuDas M, Singh A, Tilahun ME, Satyamitra MM, Wang C, Warren R, Liu CH. Unraveling links between chronic inflammation and long COVID: workshop report. J Immunol. 2024; 212(4):505-512.
24. Bohmwald K, Diethelm-Varela B, Rodr´ıguez-Guilarte L, Rivera T, Riedel CA, Gonzalez PA and Kalergis AM. Pathophysiological, immunological, and inflammatory features of long COVID. Front. Immunol. 2024; 15:1341600. doi: 10.3389/fimmu.2 024.1341600.
25. Alharbi SH. Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications. Ther Adv Endocrinol Metab. 2024; 15:20420188231222367. doi: 10.1177/20420 188231222367.
26. Ussher JR, Drucker DJ. Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nat Rev Cardiol. 2023; 20(7): 463-474. doi: 10.1038/s41569-023-00849-3.
27. Lai Y-J, Liu S-H, Manachevakul S, Lee T-A, Kuo C-T, Bello D. Biomarkers in long COVID-19: A systematic review. Front. Med. 2023. 10:1085988. doi: 10.3389/fmed.2023.1085988.
28. Wang JL & Lee CC, Ko WC. Lower risks of long COVID and mortality with GLP-1RAs in adults with type 2 diabetes: Insights into infectious, autoimmune, cardiovascular, neurological, and psychiatric diseases. 2024. Available at SSRN:
https://ssrn.com/abstract=5044989 or http://dx.doi.org/10.2139/ssrn.5044989. Accessed 12/03/25.
29. Lv R, Zhao Y, Wang X, He Y, Dong N, Min X, Liu X, Yu Q, Yuan K, Yue H, Yin Q. GLP-1 analogue liraglutide attenuates CIH-induced cognitive deficits by inhibiting oxidative stress, neuroinflammation, and apoptosis via the Nrf2/HO-1 and MAPK/NF-κB signaling pathways. Int Immunopharmacol. 2024; 142(Pt B):113222. doi: 10.1016/j.intimp.2024.113222.
30. Li Z, Zhang Z, Zhang Z, Wang Z, Li H. Cognitive impairment after long COVID-19: current evidence and perspectives. Front Neurol. 2023; 14:1239182. doi: 10.3389/fneur.2023.1239182.
31. Vadini F, Simeone PG, Boccatonda A, Guagnano MT, Liani R, Tripaldi R, Di Castelnuovo A, Cipollone F, Consoli A, Santilli F. Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study. Int J Obes (Lond). 2020; 44(6): 1254-1263. doi: 10.1038/s 4 1366-020-0535-5.
2. Yin Y, Rohli KE, Shen P, Lu H, Liu Y, Dou Q, Zhang L, Kong X, Yang S, Jia P. The epidemiology, pathophysiological mechanisms, and management toward COVID-19 patients with type 2 diabetes: a systematic review. Prim Care Diabetes. 2021; 15(6): 899-909.
3. Scirica BM, Lincoff AM, Lingvay I, Bogdanski P, Buscemi S, Colhoun H, Craciun AE, Ezhov M, Hardt-Lindberg S, Kleist Jeppesen O, Matos ALSA, Node K, Schiele F, Toplak H, van Beek A, Weeke PE, Wiviott SD, Deanfield J, Ryan D. The effect of semaglutide on mortality and COVID-19-related deaths: an analysis from the SELECT Trial. J Am Coll Cardiol. 2024; 84(17):1632-1642. doi: 10.1016/j.jac c.2024.08.007.
4. Campbell JE & Drucker DJ. Pharmacology physiology and mechanisms of incretin hormone action. Cell Metab. 2013; 17(6):819-837. doi: 10.101 6/j.cmet.2013.04.008.
5. Hammoud R & Drucker DJ. Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. Nat. Rev. Endocrinol. 2023; 19:201–216. doi: 10.1038/s41574-022-00783-3.
6. Hariyanto TI, Intan D, Hananto JE, Putri C, Kurniawan A. Pre-admission glucagon-like peptide-1 receptor agonist (GLP-1RA) and mortality from coronavirus disease 2019 (Covid-19): A systematic review, meta-analysis, and meta-regression. Diabetes Research and Clinical Practice. 2021; 179:109031. doi: 10.1016/j.diabres.2021.109031.
7. Wander PL, Lowy E, Beste LA, Tulloch-Palomino L, Korpak A, Peterson AC, Kahn SE, Boyko EJ. Prior glucose-lowering medication use and 30-day outcomes among 64,892 veterans with diabetes and COVID-19. Diabetes Care. 2021; 44(12):2708-2713.
8. Chen Y, Lv X, Lin S, Arshad M and Dai M. The association between antidiabetic agents and clinical outcomes of COVID-19 patients with diabetes: a Bayesian Network meta-analysis. Front. Endocrinol. 2022; 13:895458. doi: 10.3389/fendo.2022.895458.
9. Sudhakar M, Winfred SB, Meiyazhagan G, Venkatachalam DP. Mechanisms contributing to adverse outcomes of COVID-19 in obesity. Mol Cell Biochem. 2022; 477:1155–1193.
10. Rey-Reñones C, Martinez-Torres S, Martín-Luján FM, Pericas C, Redondo A, Vilaplana-Carnerero C, Dominguez A, Grau M. Type 2 diabetes mellitus and COVID-19: a narrative review. Biomedicines. 2022; 10(9):2089.
doi: 10.3390/biomedicines10092089.
11. Abudalo RA, Alqudah AM, Roarty C, Athamneh RY, Grieve DJ. Oxidative stress and inflammation in COVID-19: potential application of GLP-1 receptor agonists. Eur Rev Med Pharmacol Sci. 2023; 27(13): 6459-6471. doi: 10.26355/eurrev_202307_33007.
12. Mehdi SF, Pusapati S, Anwar MS, Lohana D, Kumar P, Nandula SA, Nawaz FK, Tracey K, Yang H, LeRoith D, Brownstein MJ and Roth J. Glucagon-like peptide-1: a multi-faceted anti-inflammatory agent. Front. Immunol. 2023; 14:1148209. doi: 10.3389/fim mu.2023.1148209.
13. Wang S, Ma P, Zhang S, Song S, Wang Z, Ma Y, Xu J, Wu F, Duan L, Yin Z, Luo H, Xiong N, Xu M, Zeng T, Jin Y. 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: 10.1007/s 00125-020-05209-1.
14. Holman N, Knighton P, Kar P, O'Keefe J, Curley M, Weaver A, Barron E, Bakhai C, Khunti K, Wareham NJ, Sattar N, Young B, Valabhji J. 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: 10.1016/S2213-8587(20) 30271-0.
15. Aroda VR. A review of GLP-1 receptor agonists: Evolution and advancement, through the lens of randomised controlled trials. Diabetes Obes Metab. 2018; 20 (Suppl 1):22-33. doi:10.1111/dom.13162.
16. Graña C, Ghosn L, Evrenoglou T et al. Efficacy and safety of COVID-19 vaccines. Cochrane Database Syst Rev. 2022; 12(12):CD015477. doi: 10.1002/146 51858.CD015477.
17. Greenhalgh T, Sivan M, Perlowski A, Nikolich JŽ. Long COVID: a clinical update. Lancet. 2024; 404(10453):707-724.
18. PHOSP-COVID Collaborative Group. Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. Lancet Respir Med. 2022; 10 (8):761-775. doi: 10.1016/S2213-2600(22)00127-8.
19. Su Y, Yuan D, Chen DG, Ng RH et al. (ISB-Swedish COVID-19 Biobanking Unit). Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022; 185(5):881-895.e20. doi: 10.1016/j.cell.2022.01.014.
20. Barrett CE, Koyama AK, Alvarez P, Chow W, Lundeen EA, Perrine CG, Pavkov ME, Rolka DB, Wiltz JL, Bull-Otterson L, Gray S, Boehmer TK, Gundlapalli AV, Siegel DA, Kompaniyets L, Goodman AB, Mahon BE, Tauxe RV, Remley K, Saydah S. Risk for newly diagnosed diabetes >30 days after SARS-CoV-2 infection among persons aged <18 Years - United States, March 1, 2020-June 28, 2021. MMWR Morb Mortal Wkly Rep. 2022; 71(2):59-65. doi: 10.15585/mmwr.mm7102e2.
21. Montefusco L, Ben Nasr M, D'Addio F, Loretelli C, Rossi A, Pastore I, Daniele G, Abdelsalam A, Maestroni A, Dell'Acqua M et al. Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection. Nat Metab. 2021; 3(6):774-785. doi: 10.1038/s42255-021-004 07-6.
22. Xie Y, Al-Aly Z Risks and burdens of incident diabetes in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2022; 10(5):311-321. doi: 10.101 6/S2213-8587(22)00044-4.
23. Tandon P, Abrams ND, Avula LR, Carrick DM, Chander P, Divi RL, Dwyer JT, Gannot G, Gordiyenko N, Liu Q, Moon K, PrabhuDas M, Singh A, Tilahun ME, Satyamitra MM, Wang C, Warren R, Liu CH. Unraveling links between chronic inflammation and long COVID: workshop report. J Immunol. 2024; 212(4):505-512.
24. Bohmwald K, Diethelm-Varela B, Rodr´ıguez-Guilarte L, Rivera T, Riedel CA, Gonzalez PA and Kalergis AM. Pathophysiological, immunological, and inflammatory features of long COVID. Front. Immunol. 2024; 15:1341600. doi: 10.3389/fimmu.2 024.1341600.
25. Alharbi SH. Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications. Ther Adv Endocrinol Metab. 2024; 15:20420188231222367. doi: 10.1177/20420 188231222367.
26. Ussher JR, Drucker DJ. Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nat Rev Cardiol. 2023; 20(7): 463-474. doi: 10.1038/s41569-023-00849-3.
27. Lai Y-J, Liu S-H, Manachevakul S, Lee T-A, Kuo C-T, Bello D. Biomarkers in long COVID-19: A systematic review. Front. Med. 2023. 10:1085988. doi: 10.3389/fmed.2023.1085988.
28. Wang JL & Lee CC, Ko WC. Lower risks of long COVID and mortality with GLP-1RAs in adults with type 2 diabetes: Insights into infectious, autoimmune, cardiovascular, neurological, and psychiatric diseases. 2024. Available at SSRN:
https://ssrn.com/abstract=5044989 or http://dx.doi.org/10.2139/ssrn.5044989. Accessed 12/03/25.
29. Lv R, Zhao Y, Wang X, He Y, Dong N, Min X, Liu X, Yu Q, Yuan K, Yue H, Yin Q. GLP-1 analogue liraglutide attenuates CIH-induced cognitive deficits by inhibiting oxidative stress, neuroinflammation, and apoptosis via the Nrf2/HO-1 and MAPK/NF-κB signaling pathways. Int Immunopharmacol. 2024; 142(Pt B):113222. doi: 10.1016/j.intimp.2024.113222.
30. Li Z, Zhang Z, Zhang Z, Wang Z, Li H. Cognitive impairment after long COVID-19: current evidence and perspectives. Front Neurol. 2023; 14:1239182. doi: 10.3389/fneur.2023.1239182.
31. Vadini F, Simeone PG, Boccatonda A, Guagnano MT, Liani R, Tripaldi R, Di Castelnuovo A, Cipollone F, Consoli A, Santilli F. Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study. Int J Obes (Lond). 2020; 44(6): 1254-1263. doi: 10.1038/s 4 1366-020-0535-5.