SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons?

Pitocco, Dario; Tartaglione, Linda; Viti, Luca; Leo, Mauro Di; Pontecorvi, Alfredo; Caputo, Salvatore

doi:10.1016/j.diabres.2020.108162

Cited by 26 publications

(26 citation statements)

References 18 publications

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“…Another study compared the risk of respiratory tract infections among glucose-lowering therapies and found no increased risk linked to DPP4i in T2DM patients ( Gamble et al, 2018 ). However the potential induction of leucopenia ( Pitocco et al, 2010 ), angioedema ( Gosmanov and Fontenot, 2009 ) or cough in asthma ( Baraniuk and Jamieson, 2010 ) by DPP4i represent potential pitfalls to their use as therapy in COVID-19 ( Pitocco et al, 2020 ). Although 14 years after the approval of DPP4i there have not been major safety issues related to long term use of gliptins.…”

Section: Therapeutic Potential Of Targeting Dpp4 In Diabetic Patientsmentioning

confidence: 99%

DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?

et al. 2020

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COVID-19 outbreak, caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus has become an urgent health and economic challenge. Diabetes is a risk factor for severity and mortality of COVID-19. Recent studies support that COVID-19 has effects beyond the respiratory tract, with vascular complications arising as relevant factors worsening its prognosis, then making patients with previous vascular disease more prone to severity or fatal outcome. Angiotensin-II converting enzime-2 (ACE2) has been proposed as preferred receptor for SARS-CoV-2 host infection, yet specific proteins participating in the virus entry are not fully known. SARS-CoV-2 might use other co-receptor or auxiliary proteins allowing virus infection. In silico experiments proposed that SARS-CoV-2 might bind dipeptidyl peptidase 4 (DPP4/CD26), which was established previously as receptor for MERS-CoV. The renin–angiotensin–aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes. Imbalance of the RAAS and direct effect of soluble DPP4 exert deleterious vascular effects. We hypothesize that diabetic patients might be more affected by COVID-19 due to increased presence ACE2 and DPP4 mediating infection and contributing to a compromised vasculature. Here, we discuss the role of ACE2 and DPP4 as relevant factors linking the risk of SARS-CoV-2 infection and severity of COVID-19 in diabetic patients and present an outlook on therapeutic potential of current drugs targeted against RAAS and DPP4 to treat or prevent COVID-19-derived vascular complications. Diabetes affects more than 400 million people worldwide, thus better understanding of how they are affected by COVID-19 holds an important benefit to fight against this disease with pandemic proportions.

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Section: Therapeutic Potential Of Targeting Dpp4 In Diabetic Patientsmentioning

confidence: 99%

DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?

et al. 2020

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“…It has been hypothesized that DPP4 inhibitors might be a therapeutic strategy for preventing infection and decreasing the severity of COVID-19. However, there is currently no evidence that DPP4 serves as a receptor for SARS-CoV2 [53]. Doses of other antihyperglycemic drugs such as sulfonylureas and insulin may have to be adjusted depending on blood glucose levels.…”

Section: Management Of Diabetes During the Covid-19 Pandemicmentioning

confidence: 99%

COVID-19 and diabetes: What does the clinician need to know?

Papadokostaki

Tentolouris

Liberopoulos

2020

Primary Care Diabetes

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“…It was also suggested that the higher rate of mortality and complications in patients with T2DM and MERS-CoV infection could be partly associated with a DPP4-mediated dysregulated immune response since DPP-4 is expressed in immune cells among other tissues and promotes immune cell activation [ 118 ]. Further preclinical observations have fueled an intriguing debate about whether DPP-4 inhibitors, which are commonly prescribed in patients with T2DM, might protect against SARS-CoV2 infection and mitigate COVID-19 severity [ 116 , 119 , 120 , 121 ]. It has been shown in vitro that antibodies targeted against DPP-4 can prevent the infection of human bronchial epithelial cells by the human Coronavirus-Erasmus Medical Center (hCoV-EMC) [ 117 ].…”

Section: General Recommendations For the Management Of Hyperglycemmentioning

confidence: 99%

Clinical Management of Diabetes Mellitus in the Era of COVID-19: Practical Issues, Peculiarities and Concerns

Koliaki

Tentolouris

Eleftheriadou

et al. 2020

JCM

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The management of patients with diabetes mellitus (DM) in the era of the COVID-19 pandemic can be challenging. Even if they are not infected, they are at risk of dysregulated glycemic control due to the restrictive measures which compromise and disrupt healthcare delivery. In the case of infection, people with DM have an increased risk of developing severe complications. The major principles of optimal care for mild outpatient cases include a patient-tailored therapeutic approach, regular glucose monitoring and adherence to medical recommendations regarding lifestyle measures and drug treatment. For critically ill hospitalized patients, tight monitoring of glucose, fluids, electrolytes, pH and blood ketones is of paramount importance to optimize outcomes. All patients with DM do not have an equally increased risk for severity and mortality due to COVID-19. Certain clinical and biological characteristics determine high-risk phenotypes within the DM population and such prognostic markers need to be characterized in future studies. Further research is needed to examine which subgroups of DM patients are expected to benefit the most from specific antiviral, immunomodulatory and other treatment strategies in the context of patient-tailored precision medicine, which emerges as an urgent priority in the era of COVID-19.

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SARS-CoV-2 and DPP4 inhibition: Is it time to pray for Janus Bifrons?

Cited by 26 publications

References 18 publications

DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?

DPP4 and ACE2 in Diabetes and COVID-19: Therapeutic Targets for Cardiovascular Complications?

COVID-19 and diabetes: What does the clinician need to know?

Clinical Management of Diabetes Mellitus in the Era of COVID-19: Practical Issues, Peculiarities and Concerns

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