Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population. RESEARCH DESIGN AND METHODS In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation <95% when breathing ambient air or when receiving oxygen support. The primary end points were discharge from the hospital/death and improvement of clinical outcomes, defined as an increase in at least two points on a seven-category modified ordinal scale. Data were collected retrospectively from patients receiving sitagliptin from 1 March through 30 April 2020. RESULTS Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29-0.66]; P 5 0.0001), with an improvement in clinical outcomes (60% vs. 38% of improved patients; P 5 0.0001) and with a greater number of hospital discharges (120 vs. 89 of discharged patients; P 5 0.0008) compared with patients receiving standard of care, respectively. CONCLUSIONS In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.

Aims SARS-CoV-2 causes severe respiratory syndrome (COVID-19) with high mortality due to a direct cytotoxic viral effect and a severe systemic inflammation. We are herein discussing a possible novel therapeutic tool for COVID-19. Methods Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. Results The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. Conclusions The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.

Our data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED.

Background-Erectile dysfunction (ED) is associated with coronary artery disease (CAD). In diabetic patients, CAD is often silent. Among diabetic patients with silent CAD, the prevalence of ED has never been evaluated. We investigated whether ED is associated with asymptomatic CAD in type 2 diabetic patients. Methods and Results-We evaluated the prevalence of ED in 133 uncomplicated diabetic men with angiographically verified silent CAD and in 127 diabetic men without myocardial ischemia at exercise ECG, 48-hour ambulatory ECG, and stress echocardiography. The groups were comparable for age and diabetes duration. Patients were screened for ED using the validated International Index of Erectile Function (IIEF-5) questionnaire. The prevalence of ED was significantly higher in patients with than in those without silent CAD (33.8% versus 4.7%; Pϭ0.000). Multiple logistic regression analysis showed that ED, apolipoprotein(a) polymorphism, smoking, microalbuminuria, HDL, and LDL were significantly associated with silent CAD; among these risk factors, ED appeared to be the most efficient predictor of silent CAD (OR, 14.8; 95% CI, 3.8 to 56.9). Conclusions-Our study first shows a strong and independent association between ED and silent CAD in apparently uncomplicated type 2 diabetic patients. If our findings are confirmed, ED may become a potential marker to identify diabetic patients to screen for silent CAD. Moreover, the high prevalence of ED among diabetics with silent CAD suggests the need to perform an exercise ECG before starting a treatment for ED, especially in patients with additional cardiovascular risk factors.