ACE2 and SARS-CoV-2 Infection: Might GLP-1 Receptor Agonists Play a Role?

Abstract

Recently it has been hypothesized that DPP4 inhibitors can have a beneficial effect on SARS-CoV-2 infection through immunoregulating activity.Experimental study on streptozotocintreated rats showed that liraglutide was able to stimulate the expression of pulmonary angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7).Liraglutide modulated different elements of the renin angiotensin system (RAS), significantly increasing ACE2 and Mas receptor (MasR) mRNA expression in pup lungs from food-restricted mothers. Some action mechanisms support the hypothesis of a protective action of GLP-1R agonists, capable of mitigating a more serious clinical course among SARS-CoV-2-infected individuals with T2DM.Type 2 diabetes mellitus (T2DM) represents an important risk factor for a more severe evolution associated with higher lethality of the infection from the new coronavirus disease 2019 (COVID-19; caused by severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), responsible for the current pandemic that originated from the epidemic which initially affected the Wuhan region in China in December 2019 [1]. SARS-CoV-2 uses as a receptor for the infection of respiratory epithelial cells-the angiotensinconverting enzyme 2 (ACE2) receptor [1]; this was also the case for SARS coronavirus (SARS-CoV), responsible for the epidemic that affected more than 8000 people mainly in Asia during the 2002-2003 period [2]. In contrast, Middle East respiratory syndrome (MERS) coronavirus, which caused (as of November 2019) 2494 confirmed cases of infection reported to the World Digital Features To view digital features for this article go to

SGLT‐2 inhibitors and the risk of hospitalization for community‐acquired pneumonia: A population‐based cohort study

“…Indeed, several studies have reported protective associations between the use of GLP-1 RA and respiratory function [31][32][33] and risk of infections. 34 Second, it is also possible that the observed protective association is the result of an increased risk of pneumonia with DPP-4i. However, although there may be a biological mechanism linking DPP-4i to an increased risk of infections, [35][36][37] most previous studies of the pneumonia risk of DPP-4i did not identify an increased risk, [21][22][23][24][25]38 suggesting that this is an unlikely explanation for the observed association.…”

Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England

“…7 Similarly, GLP-1 receptor agonists have been associated with increased ACE2 expression in lungs and heart tissue and with beneficial effects in acute lung injury, with suggestions of possible helpful and harmful effects in COVID-19. 8,9 Recent studies have suggested a lower risk of COVID-19-related hospital mortality in people with type 2 diabetes who were prescribed metformin before hospital admission 10 or sitagliptin on admission. 11 Notwithstanding calls for ongoing scrutiny to understand the use, risks, and benefits of individual classes of glucoselowering drugs in people with type 2 diabetes and COVID-19, there are no comprehensive, comparative data on differential effects of glucose-lowering drugs on risk for severe COVID-19.…”

“… 7 Similarly, GLP-1 receptor agonists have been associated with increased ACE2 expression in lungs and heart tissue and with beneficial effects in acute lung injury, with suggestions of possible helpful and harmful effects in COVID-19. 8 , 9 Recent studies have suggested a lower risk of COVID-19-related hospital mortality in people with type 2 diabetes who were prescribed metformin before hospital admission 10 or sitagliptin on admission. 11 …”

Glucagon‐like peptide‐1 receptor agonists in the era of COVID‐19: Friend or foe?

“…Besides being important glucose‐lowering agents, GLP‐1RAs pose promising anti‐inflammatory and anti‐obesogenic properties, pulmonary protective effects, as well as beneficial impact on gut microbiome composition. In conclusion, taking everything previously mentioned into consideration, GLP‐1RAs seem to be potential candidates for the treatment of patients, affected by COVID‐19 infection, with or even without type 2 diabetes mellitus, as well as excellent antidiabetic (glucose‐lowering) agents during COVID‐19 pandemic times 70 . Last but not least, it is of high importance to constantly evaluate new scientific data/evidence regarding pharmacotherapy in COVID‐19 pandemic times, based on evidence‐based medicine principles.…”