OBJECTIVE: Dipeptidyl peptidase-4 inhibitors (DPP4i) have been recently 
associated with increased risk of pancreatitis and cancer. The aim of the 
present meta-analysis of randomized clinical trials is the assessment of the 
effect of DPP4i on the incidence of major cardiovascular events (MACE), cancer, 
and pancreatitis.
RESEARCH DESIGN AND METHODS: An extensive Medline and Embase search for 
'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 
'dutogliptin' was performed, collecting all randomized clinical trials on humans 
up to March 1, 2011. The present meta-analysis was therefore performed including 
all randomized clinical trials with a duration of at least 24 weeks, enrolling 
patients with type 2 diabetes, comparing DPP4i with either placebo or active 
drugs. Completed but still unpublished trials were identified through a search 
of www.clinicaltrials.gov, Food and Drug Administration, and European Medicines 
Agency website.
RESULTS: Fifty-three trials enrolling 20,312 and 13,569 patients for DPP4i and 
comparators, respectively, were included, reporting 176 malignancies, 257 MACE, 
and 22 pancreatitis. DPP4i, compared with placebo or other treatment, were 
associated with a similar risk of cancer (MH-OR 1.020 [0.742-1.402]; p = 0.90) 
and pancreatitis (0.786 [0.357-1.734], p = 0.55), and with a reduced risk of 
MACE (MH-OR 0.689 [0.528-0.899], p = 0.006).
CONCLUSIONS: The present meta-analysis seems to exclude any relevant short term 
effect of DPP4i on the incidence of cancer and suggest a possible protection 
from cardiovascular events. This result should be interpreted with caution, as 
those events were not the principal endpoint, the trial duration was short, and 
the characteristics of patients included could be different from routine 
clinical practice.