Abstract
The fast spread of coronavirus 2019 (COVID-19) calls for immediate action to counter the associated significant loss of human life and deep economic impact. Certain patient populations like those with obesity and diabetes are at higher risk for acquiring severe COVID-19 disease and have a higher risk of COVID-19 associated mortality. In the absence of an effective and safe vaccine, the only immediate promising approach is to repurpose an existing approved drug. Several drugs have been proposed and tested as adjunctive therapy for COVID-19. Among these drugs are the glucagon-like peptide-1 (GLP-1) 2 agonists and the dipeptidylpeptidase-4 (DPP-4) inhibitors. Beyond their glucose-lowering effects, these drugs have several pleiotropic protective properties, which include cardioprotective effects, anti-inflammatory and immunomodulatory activities, antifibrotic effects, antithrombotic effects, and vascular endothelial protective properties. This narrative review discusses these protective properties and addresses their scientific plausibility for their potential use as adjunctive therapy for COVID-19 disease.
Keywords: GLP-1, ACE-2, COVID-19, DPP-4, cardioprotective effects, immunomodulatory.
Graphical Abstract
[http://dx.doi.org/10.4093/dmj.2020.0206] [PMID: 33752274]
[http://dx.doi.org/10.1177/1932296820924469] [PMID: 32389027]
[http://dx.doi.org/10.1007/s00125-020-05209-1]
[http://dx.doi.org/10.1111/imm.12394] [PMID: 25262977]
[http://dx.doi.org/10.2217/imt-2020-0349] [PMID: 33906375]
[http://dx.doi.org/10.1016/j.jhep.2020.09.031] [PMID: 33038433]
[http://dx.doi.org/10.1089/wound.2020.1309] [PMID: 33035150]
[http://dx.doi.org/10.1016/S0140-6736(06)69705-5] [PMID: 17098089]
[http://dx.doi.org/10.1111/jcmm.15674] [PMID: 32713161]
[http://dx.doi.org/10.1111/dom.14329] [PMID: 33502076]
[http://dx.doi.org/10.2337/dci20-0035] [PMID: 32958627]
[http://dx.doi.org/10.2337/dc20-1521] [PMID: 32994187]
[http://dx.doi.org/10.2337/dc20-1824] [PMID: 33547204]
[http://dx.doi.org/10.2337/dc20-1340] [PMID: 33023989]
[http://dx.doi.org/10.1021/acs.molpharmaceut.9b00308]
[http://dx.doi.org/10.1111/j.1463-1326.2012.01663.x] [PMID: 22776039]
[http://dx.doi.org/10.3389/fendo.2019.00080] [PMID: 30828317]
[http://dx.doi.org/10.1016/j.it.2008.02.010] [PMID: 18456553]
[http://dx.doi.org/10.1155/2018/6920620] [PMID: 30627159]
[http://dx.doi.org/10.1155/2016/3094642] [PMID: 27110066]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.117.028136] [PMID: 28847797]
[http://dx.doi.org/10.3390/ijms160920195] [PMID: 26343632]
[http://dx.doi.org/10.1007/s00592-020-01539-z] [PMID: 32506195]
[http://dx.doi.org/10.1152/ajprenal.00590.2014] [PMID: 25656369]
[http://dx.doi.org/10.1186/s12885-019-6231-y] [PMID: 31664952]
[http://dx.doi.org/10.1155/2018/6091014] [PMID: 30186862]
[http://dx.doi.org/10.3389/fendo.2012.00112] [PMID: 22973260]
[http://dx.doi.org/10.1186/s13098-016-0169-x] [PMID: 27462372]
[http://dx.doi.org/10.1016/j.taap.2017.08.005] [PMID: 28807765]
[http://dx.doi.org/10.1016/j.lfs.2019.117152] [PMID: 31837333]
[http://dx.doi.org/10.1016/j.metabol.2014.06.004] [PMID: 25034387]
[http://dx.doi.org/10.1016/j.diabres.2020.108163] [PMID: 32333972]
[http://dx.doi.org/10.1016/j.diabres.2020.108216] [PMID: 32416120]
[http://dx.doi.org/10.1111/dom.14324] [PMID: 33528920]
[http://dx.doi.org/10.1210/en.2014-1685] [PMID: 26196539]
[http://dx.doi.org/10.2337/dc20-0643] [PMID: 32430459]
[http://dx.doi.org/10.3390/ijms18030563] [PMID: 28273875]
[http://dx.doi.org/10.1097/PCC.0b013e3182a55735] [PMID: 24226567]
[http://dx.doi.org/10.1007/s10557-015-6592-7] [PMID: 25994830]
[http://dx.doi.org/10.1182/blood-2012-09-459156] [PMID: 23386129]
[http://dx.doi.org/10.1002/emmm.201000080] [PMID: 20597104]
[http://dx.doi.org/10.1038/nm1267] [PMID: 16007097]
[http://dx.doi.org/10.1080/1061186X.2020.1797754] [PMID: 32700580]
[http://dx.doi.org/10.3389/fphar.2020.00432] [PMID: 32322207]
[http://dx.doi.org/10.2337/dc20-0941] [PMID: 32409501]
[http://dx.doi.org/10.1016/j.ejphar.2016.10.016] [PMID: 27756605]
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[http://dx.doi.org/10.1038/s41374-018-0170-0] [PMID: 30659271]
[http://dx.doi.org/10.3389/fimmu.2020.01580] [PMID: 32670297]
[http://dx.doi.org/10.1016/j.jaci.2018.01.053] [PMID: 29678751]
[http://dx.doi.org/10.1016/j.intimp.2015.08.043] [PMID: 26362207]
[http://dx.doi.org/10.1016/j.lfs.2019.117017] [PMID: 31678284]
[http://dx.doi.org/10.1002/art.41058] [PMID: 31350829]
[http://dx.doi.org/10.1002/dmrr.3330] [PMID: 32336007]
[http://dx.doi.org/10.2337/db15-0084] [PMID: 26294429]
[http://dx.doi.org/10.1210/er.2011-1052] [PMID: 22323472]
[http://dx.doi.org/10.2337/db15-1141] [PMID: 26936963]
[http://dx.doi.org/10.1186/1475-2840-12-154] [PMID: 24148218]
[http://dx.doi.org/10.1007/s00125-010-1831-8] [PMID: 20593161]
[http://dx.doi.org/10.1177/1479164111404257] [PMID: 21562063]
[http://dx.doi.org/10.1007/s00395-015-0465-x] [PMID: 25600227]
[http://dx.doi.org/10.2337/dbi16-0014] [PMID: 27222394]
[http://dx.doi.org/10.1161/CIRCRESAHA.114.301958] [PMID: 24855202]
[http://dx.doi.org/10.1136/heartjnl-2020-317056] [PMID: 32354800]
[http://dx.doi.org/10.1016/j.clinthera.2014.11.008] [PMID: 25554560]
[http://dx.doi.org/10.1097/MOL.0b013e32834d68f0] [PMID: 22123671]
[http://dx.doi.org/10.3389/fendo.2018.00672] [PMID: 30532733]
[http://dx.doi.org/10.1177/1479164112449562] [PMID: 22732108]
[http://dx.doi.org/10.1177/1479164112440816] [PMID: 22496404]
[http://dx.doi.org/10.1210/er.2014-1035] [PMID: 25216328]
[http://dx.doi.org/10.1016/j.ajem.2020.04.048] [PMID: 32317203]
[http://dx.doi.org/10.1038/s41569-020-0360-5] [PMID: 32139904]
[http://dx.doi.org/10.1038/s41569-020-0413-9] [PMID: 32690910]
[http://dx.doi.org/10.1001/jamacardio.2020.1286]
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]