Sitagliptin Treatment in Diabetic COVID-19 Positive Patients

Summary

Coronavirus Pathology is frequently associated with both diabetes mellitus and metabolic syndrome. In particular, results of observational studies and meta-analyzes configure diabetes as one of the main risk factors for the development of complications and unfavorable course of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome), the syndromes caused respectively by SARS- VOC coronavirus and MERS-COV coronavirus. The available data confirm this association also in the clinical picture of the infection supported by SARS-COV 2 (COVID-19). In the epidemic outbreak that erupted 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%). At the moment, the mainly involved pathophysiological molecular mechanisms are not clearly defined. It has been hypothesized that the transmembrane glycoprotein type II CD26, known for the enzyme activity Dipeptilpeptidase 4 exerted by its extracellular domain, may play a fundamental role in this process. In addition, it is considerably expressed at the parenchyma and lung interstitium level and carries out both systemic and paracrine enzymatic activity, modulating the activity of various proinflammatory cytokines, growth factors and vasoactive peptides at the level of the deep respiratory tract. The pulmonary parenchyma and the interstitium express significantly the Dipeptilpeptidase 4 protein, which in the Middle East Respiratory Syndrome favors the entry of the virus into the cells, thus allowing the virus to replicate within the cells and thus spread throughout the cell inside the organism. Dipeptilpeptidase 4 regulates the function of bioactive peptides and above all of cytokines, vasoactive peptides and chemokines present at the level of the mesothelium, of the deep respiratory tract (alveolar epithelium and alveolar bronchus), of endothelial and immune cells triggering the inflammatory storm. In line with this evidence, it has been hypothesized that acute respiratory disease from Coronavirus may depend on the massive localization of Dipeptilpeptidase 4 in lung tissue. Furthermore, the involvement of Dipeptilpeptidase 4 in other chronic respiratory diseases has been demonstrated. Starting from these observations we hypothesized that the selective blockade of Dipeptilpeptidase 4 can favorably modulate the pulmonary inflammatory response in the subject affected by COVID-19. Among the drugs that selectively block Dipeptilpeptidase 4, the one with greater affinity precisely for Dipeptilpeptidase 4 is Sitagliptin.

Conditions

• Covid19

Interventions

DRUG

Retrospective case-control analysis

Evaluation of clinical, laboratory and instrumental parameters of diabetic patients during hospitalization for COVID-19. The data will be extracted anonymously from the computerized medical records commonly used in clinical practice by the centers involved in the study

Sponsors & Collaborators

• Papa Giovanni XXIII Hospital

  collaborator OTHER

• Fondazione IRCCS Policlinico San Matteo di Pavia

  collaborator OTHER

• Humanitas Hospital, Italy

  collaborator OTHER

• Ospedale dell'Angelo, Venezia-Mestre

  collaborator OTHER

• University of Pavia

  collaborator OTHER

• University of Milan

  lead OTHER

Principal Investigators

• Paolo Fiorina, MD, PhD · ASST FBF Sacco

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-05-14

Primary Completion

2020-06-15

Completion

2020-06-15

FDA Drug

Yes

Countries

• Italy

Study Locations