title: Safety of dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized clinical trials.
abstract: 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.
  
  
  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 Completed but still unpublished trials were identified through a search of www.clinicaltrials.gov, Food and Drug Administration, and European Medicines Agency website.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.
authors: Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, Careggi Teaching Hospital, Florence, Italy.
authors: Matteo
authors: M
authors: Monami
authors: Ilaria
authors: I
authors: Dicembrini
authors: Daniele
authors: D
authors: Martelli
authors: Edoardo
authors: E
authors: Mannucci
mesh_terms: D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D015994:Incidence; D020407:Internet; D016239:MEDLINE; D008297:Male; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology*; D010195:Pancreatitis / Q000139:chemically induced / Q000453:epidemiology*; D011897:Random Allocation; D012307:Risk Factors; D013997:Time Factors
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors