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.

The investigators propose a randomized controlled open label intervention study. Patients hospitalized for COVID-19 and affected by type 2 diabetes mellitus will be included in the study and divided into two groups by randomization: sitagliptin add-on standard of care therapy with nutritional therapy with or without insulin treatment (study group) vs nutritional therapy with or without insulin treatment (group of control, standard therapy). The design of the study provides an open randomization to allow its feasibility in times compatible with the achievement of adequate cases during the epidemic. The presence of placebo and a double-blind study, would lead to longer planning and enrollment times.

Patients with type 2 diabetes mellitus hospitalized for COVID-19 and randomized to the study group will be treated with sitagliptin at an adjusted dosage for estimated glomerular filtrate: 100 mg once daily (estimated glomerular filtration rate less than or equal to 45 mL / min / 1.73 m2) or 50 mg (estimated glomerular filtration rate 30-45 mL / min / 1.73 m2) in combination or not with insulin treatment. Patients with stage IV and V renal impairment (estimated glomerular filtration rate less than or equal to 30 mL / min / 1.73 m2) will be excluded. Enrolled patients will be followed according to the following scheme:

Time points:

• T0: The doctor explains the protocol to the patient and he gives to him the informed consent and the letter to the general practitioner.
• T1: The patient gives the signed and dated consent and officially enters the study. Basic assessments will be made. At the baseline, the clinical response, the main laboratory and instrumental tests will be taken into consideration. Biological samples will be taken for immunological study. Diabetic patients will begin treatment with Sitagliptin 100 or 50 mg add-on to nutritional therapy and, eventually, insulin treatment. Any other hypoglycemic agents taken before admission will be suspended.
• T2: 7 days after T1, for both groups of patients, evaluation of the clinical response, of the average daily blood glucose levels, of the main laboratory and instrumental tests.
• T3: 10 days after T2, for both groups of patients, evaluation of clinical response, average daily blood glucose levels, of the main laboratory and instrumental tests. Collection of biological samples for immunological study. End of the study.

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