The Effect of Sitagliptin Treatment in COVID-19 Positive Diabetic Patients

• Status: Not yet recruiting
• Trial end date: 2022-12-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Milan
• Treatments: Sitagliptin Phosphate

Criteria

Inclusion Criteria:

• Diagnosis of type 2 diabetes, according to ADA 2020 criteria

• HbA1c levels at the entrance or in the two previous months <9%

• Diagnosis of Covid-19 (swab for positive SARS-COV2 RNA) with pneumonia, with or without increase in inflammation indexes, with or without respiratory failure

• No indication for tocilizumab therapy (BCRSS, Brescia Covid Respiratory Severity Scale, <3).

• Written and dated informed consent from the patient or his legally valid representative

Exclusion Criteria:

• Pregnancy

• Type 1 diabetes

• Stage IV and V renal failure (stimated glomerular filtration rate <30 ml / min)

• Treatment with Dipeptidyl peptidase-4 inhibitors or GLP-1 Receptor Agonists in the month prior to hospitalization

• Pioglitazone treatment in the month prior to hospitalization

• Treatment in the month preceding or in the course of hospitalization with "biological" drugs for immuno-rheumatological diseases (in particular tocilizumab)

• Presence of other acute or chronic ongoing infections

• Neurological or psychiatric diseases, diagnosis of hemoglobinopathy, diagnosis of liver disease, cancer, cystic fibrosis or malabsorption syndrome

• Dysphagia with need for artificial nutrition

• Positive history of acute and chronic pancreatitis

• Unstable cardiovascular disease or known atherosclerotic disease

• A history of alcohol or drug abuse

• Known human immunodeficiency virus (HIV) or hepatitis

• Presence of serious diseases or conditions that make the patient unsuitable for the study

• Surgery in the previous two weeks