question: AIM: Concerns have been raised that dipeptidyl-peptidase 4 inhibitors (DPP-4i) may increase the risk of pneumonia. We analysed observational data and clinical trials to explore whether use of DPP-4i modifies the risk of pneumonia. METHODS: We identified patients with diabetes in the Veneto region administrative database and performed propensity score matching between new users of DPP-4 inhibitors and new users of other oral glucose-lowering medications (OGLMs). We compared the rate of hospitalization for pneumonia between matched cohorts using the Cox proportional hazard model. The same analysis was repeated using the database of a local diabetes outpatient clinic. We retrieved similar observational studies from the literature to perform a meta-analysis. Results from trials reporting pneumonia rates among patients randomized to DPP-4 inhibitors versus placebo/active comparators were also meta-analysed. RESULTS: In the regional database, after matching 6495 patients/group, new users of DPP-4 inhibitors had a lower rate of hospitalization for pneumonia than new users of other OGLMs (HR 0.76; 95% CI 0.61-0.95). In the outpatient database, after matching 867 patients/group, new users of DPP-4 inhibitors showed a non-significantly lower rate of hospitalization for pneumonia (HR 0.65; 95% CI 0.41-1.04). The meta-analysis of observational studies yielded an overall non-significant lower risk of hospitalization for pneumonia among DPP-4 inhibitor users (RR 0.81; 95% CI 0.65-1.01). The meta-analysis of randomized controlled trials showed no overall effect of DPP-4 inhibitors on pneumonia risk (RR 1.06; 95% CI 0.93-1.20). CONCLUSION: The use of DPP-4 inhibitors can be considered as safe with regard to the risk of pneumonia.