Is DPP4 inhibition a comrade or adversary in COVID-19 infection

Dalan, Rinkoo

doi:10.1016/j.diabres.2020.108216

Cited by 29 publications

(35 citation statements)

References 19 publications

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“…These findings are consistent with literature suggesting that DPP-4/CD26 may interact with the S1 domain of the viral spike glycoprotein (39), which has been established as SARS-CoV-2's molecular link with the ACE-2 receptor expressed on the cells surface (40). The DPP4 inhibition may play a role in antagonizing the DPP4/CD26 inflammatory pathway, reducing COVID-19 virulence, and preventing the dangerous cytokine storm started at pulmonary levels, which is involved in disease progression (41,42).…”

Section: Discussionmentioning

confidence: 94%

Impact of Comorbidities and Glycemia at Admission and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes With COVID-19: A Case Series From an Academic Hospital in Lombardy, Italy

et al. 2020

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Diabetes may unfavorably influence the outcome of coronavirus disease 19 (COVID-19), but the determinants of this effect are still poorly understood. In this monocentric study, we aimed at evaluating the impact of type 2 diabetes, comorbidities, plasma glucose levels, and antidiabetes medications on the survival of COVID-19 patients. RESEARCH DESIGN AND METHODS This was a case series involving 387 COVID-19 patients admitted to a single center in the region of Lombardy, the epicenter of the severe acute respiratory syndrome coronavirus 2 pandemic in Italy, between 20 February and 9 April 2020. Medical history, pharmacological treatments, laboratory findings, and clinical outcomes of patients without diabetes and patients with type 2 diabetes were compared. Cox proportional hazards analysis was applied to investigate risk factors associated with mortality. RESULTS Our samples included 90 patients (23.3%) with type 2 diabetes, who displayed double the mortality rate of subjects without diabetes (42.3% vs. 21.7%, P < 0.001). In spite of this, after correction for age and sex, risk of mortality was significantly associated with a history of hypertension (adjusted hazard ratio [aHR] 1.84, 95% CI 1.15-2.95; P 5 0.011), coronary artery disease (aHR 1.56, 95% CI 1.04-2.35; P 5 0.031), chronic kidney disease (aHR 2.07, 95% CI 1.27-3.38; P 5 0.003), stroke (aHR 2.09, 95% CI 1.23-3.55; P 5 0.006), and cancer (aHR 1.57, 95% CI 1.08-2.42; P 5 0.04) but not with type 2 diabetes (P 5 0.170). In patients with diabetes, elevated plasma glucose (aHR 1.22, 95% CI 1.04-1.44, per mmol/L; P 5 0.015) and IL-6 levels at admission (aHR 2.47, 95% CI 1.28-4.78, per 1-SD increase; P 5 0.007) as well as treatments with insulin (aHR 3.05, 95% CI 1.57-5.95; P 5 0.001) and b-blockers (aHR 3.20, 95% CI 1.50-6.60; P 5 0.001) were independently associated with increased mortality, whereas the use of dipeptidyl peptidase 4 inhibitors was significantly and independently associated with a lower risk of mortality (aHR 0.13, 95% CI 0.02-0.92; P 5 0.042). CONCLUSIONS Plasma glucose levels at admission and antidiabetes drugs may influence the survival of COVID-19 patients affected by type 2 diabetes.

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Section: Discussionmentioning

confidence: 94%

Impact of Comorbidities and Glycemia at Admission and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes With COVID-19: A Case Series From an Academic Hospital in Lombardy, Italy

et al. 2020

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“…Dipeptidyl peptidase-4 inhibitors (DPP4i) are antidiabetic drugs that act indirectly enhances incretin hormone actions in a diffuse manner, leading to positive actions in the inflammatory, immunologic, and vascular systems, and consequently has been proposed to be potential candidates against COVID-19 [306,[316][317][318], currently being tested in two clinical trials. Besides the attenuation of angiotensin II activity [318], DPP4i may also prevent acute lung injury in response to different stressors [319][320][321][322][323][324] and has shown inhibitory effects on other coronaviruses, including the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) [325][326][327], which could play protective role in the first and second stages of COVID-19 [328]. Currently, there are four clinical trials testing DPP4i for COVID-19, including two with sitagliptin and two with linagliptin [329][330][331].…”

Section: Of Minor Relevancementioning

confidence: 99%

Repurposing existing drugs for COVID-19: an endocrinology perspective

Cadegiani

2020

BMC Endocr Disord

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Background Coronavirus Disease 2019 (COVID-19) is a multi-systemic infection caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), that has become a pandemic. Although its prevailing symptoms include anosmia, ageusia, dry couch, fever, shortness of brief, arthralgia, myalgia, and fatigue, regional and methodological assessments vary, leading to heterogeneous clinical descriptions of COVID-19. Aging, uncontrolled diabetes, hypertension, obesity, and exposure to androgens have been correlated with worse prognosis in COVID-19. Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2. Main text While safe and effective therapies for COVID-19 lack, the current moment of pandemic urges for therapeutic options. Existing drugs should be preferred over novel ones for clinical testing due to four inherent characteristics: 1. Well-established long-term safety profile, known risks and contraindications; 2. More accurate predictions of clinical effects; 3. Familiarity of clinical management; and 4. Affordable costs for public health systems. In the context of the key modulators of SARS-CoV-2 infectivity, endocrine targets have become central as candidates for COVID-19. The only endocrine or endocrine-related drug class with already existing emerging evidence for COVID-19 is the glucocorticoids, particularly for the use of dexamethasone for severely affected patients. Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat). Several other candidates show less consistent plausibility. In common, except for dexamethasone, all candidates have no evidence for COVID-19, and clinical trials are needed. Conclusion While dexamethasone may reduce mortality in severely ill patients with COVID-19, in the absence of evidence of any specific drug for mild-to-moderate COVID-19, researchers should consider testing existing drugs due to their favorable safety, familiarity, and cost profile. However, except for dexamethasone in severe COVID-19, drug treatments for COVID-19 patients must be restricted to clinical research studies until efficacy has been extensively proven, with favorable outcomes in terms of reduction in hospitalization, mechanical ventilation, and death.

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“…Human DPP-4 transgenic diabetic mice exhibit prolonged severe disease and immune dysregulation following MERS-Cov infection [40] . However, Rinkoo Dalan presents that DPP-4 inhibitors might not be beneficial to COVID-19 infection for the following reasons: (1) DPP-4i may not effectively reduce infection transmission; (2) DPP-4i may be a disadvantage for suppressing T cell immunity; (3) DPP-4i may increase fibrotic lesion in the lung; (4) DPP-4i recruits regenerative stem cells; (5) DPP-4i is related to a prothrombotic state [41] . To date there is no direct consequences between COVID-19 infection and DPP-4 inhibitors.…”

Section: Discussionmentioning

confidence: 99%