The Effect of Sitagliptin Treatment in COVID-19 Positive Diabetic Patients
Status:
Not yet recruiting
Trial end date:
2022-12-30
Target enrollment:
Participant gender:
Summary
The COVID-19 pathology is frequently associated with diabetes mellitus and metabolic
syndrome. In the epidemic outbreak that exploded at the beginning of 2020 in the Lombardy
Region, about two thirds of the patients who died from COVID-19 were affected by diabetes
mellitus. COVID-19 occurs in 70% of cases with an inflammatory pathology of the airways that
can be fed by a cytokine storm and result in severe respiratory failure (10% cases) and death
(5%). The pathophysiological molecular mechanisms are currently not clearly defined. It is
hypothesized that the transmembrane glycoprotein type II CD26, known for the enzyme activity
Dipeptilpeptidase 4 of the extracellular domain, may play a main role in this condition. It
is in fact considerably expressed at the level of parenchyma and pulmonary interstitium and
carries out both systemic and paracrine enzymatic activity, modulating the function of
various proinflammatory cytokines, growth factors and vasoactive peptides in the deep
respiratory tract. Of particular interest is the fact that Dipeptilpeptidase 4 has been
identified as a cellular receptor for S glycoprotein of MERS-COV. In the case of the SARS-COV
2 virus, the main receptor is the Angiotensin-Converting Enzyme 2 protein, but a possible
interaction with Dipeptilpeptidase 4 also cannot be excluded. The selective blockade of
Dipeptilpeptidase 4 could therefore favorably modulate the pulmonary inflammatory response in
the subject affected by COVID-19. This protein is also known for the enzymatic degradation
function of the native glucagon-like peptide 1, one of the main regulators of insulin
secretion. This is why it is a molecular target in the treatment of diabetes (drugs that
selectively inhibit Dipeptilpeptidase 4 are marketed with an indication for the treatment of
type 2 diabetes). It is believed that the use of a Dipeptilpeptidase 4 inhibitor in people
with diabetes and hospitalized for Covid-19 may be safe and of particular interest for an
evaluation of the effects on laboratory and instrumental indicators of inflammatory lung
disease. Among the drugs that selectively block Dipeptilpeptidase 4, the one with the
greatest affinity is Sitagliptin.