title: Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  Preliminary data from randomized trials with metabolic outcomes have shown that treatment with dipeptidyl peptidase-4 inhibitors (DPP4i) could be associated with a reduced incidence of major cardiovascular events (MACE). The present meta-analysis is aimed at verifying this protective effect, collecting all available data from randomized trials.
  
  
  METHODS
  A comprehensive search for published and unpublished trials with a duration ≥24 weeks comparing DPP4i with placebo or other drugs was performed, retrieving all MACE reported as serious adverse events together with death from any cause. Mantel-Haenzel odds ratio (MH-OR) was calculated with random effect models for MACE, myocardial infarction, stroke and mortality. When available, effects on glycated haemoglobin, lipid profile and blood pressure were also assessed and used for the estimation of the modification of risk for myocardial infarction using the UKPDS risk engine.
  
  
  RESULTS
  A total of 70 trials, enrolling 41 959 patients with a mean follow-up of 44.1 weeks, was collected and included in the analysis. The MH-OR (95% Confidence Interval) was 0.71[0.59;0.86], 0.64[0.44;0.94], 0.77[0.48;1.24] and 0.60[0.41;0.88] for MACE, myocardial infarction, stroke and mortality, respectively.
  
  
  CONCLUSIONS
  Treatment with DPP4i reduces the risk of cardiovascular events (particularly myocardial infarction) and all-cause mortality in patients with type 2 diabetes. The reduction in the incidence of myocardial infarction is greater than what predicted on the basis of conventional risk factors, suggesting a role for other mechanisms.
authors.affiliation: Section of Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Florence, Italy. mmonami@libero.it
authors.forename: M
authors.initials: M
authors.lastname: Monami
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
authors.forename: I
authors.initials: I
authors.lastname: Dicembrini
authors.forename: E
authors.initials: E
authors.lastname: Mannucci
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D015994:Incidence; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000517:prevention & control*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human