title: Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in diabetic patients: A meta-analysis.
abstract: BACKGROUND
  Dipeptidyl peptidase-4 inhibitors (DPP-4is) improve glucose control in patients with type 2 diabetes mellitus (DM); however, only few studies were properly designed to evaluate their cardiovascular (CV) effects. The purpose of this study was to assess the impact of DPP-4i treatment on CV morbidity and mortality.
  
  
  METHODS
  Randomized clinical trials enrolling more than 200 patients, comparing DPP-4 versus placebo or active treatments in patients with DM and reporting at least one event among all-cause and CV mortality, myocardial infarction (MI), stroke and new onset of heart failure (HF) were included in the analysis.
  
  
  RESULTS
  Ninety-four trials enrolling 85,224 patients (median follow-up=29weeks) were included in the analysis. Compared to control, treatment with DPP-4i did not affect all-cause and CV mortality, as well as stroke, in the short and long terms (< and >=29weeks, respectively). DPP-4i reduced the risk of MI in the short (RR: 0.584 [95% CI: 0.361 to 0.943]; p=0.028), but not in the long term. Additionally, long-term treatment with DPP-4 was associated with a 15.8% increased risk of HF (RR: 1.158 [CI: 1.011 to 1.326]; p=0.034). No heterogeneity among studies or publication bias was detected.
  
  
  CONCLUSIONS
  DPP4is do not affect all cause- and CV-mortality and stroke in diabetic patients; the reduction in MI observed with short-term treatment does not persist in the long term. Long-term use of DPP-4i in diabetic patients is associated with increased risk of HF.
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; IRCCS San Raffaele Roma, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Savarese
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Perrone-Filardi
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: D'Amore
authors.affiliation: IRCCS San Raffaele Roma, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: Italian Medicines Agency (AIFA), Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
authors.affiliation: IRCCS San Raffaele Roma, Italy; Cardiovascular and Cell Sciences Research Institute, St George's University, London, UK. Electronic address: giuseppe.rosano@gmail.com.
authors.forename: Giuseppe M C
authors.initials: GM
authors.lastname: Rosano
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors
keywords: Cardiovascular; DPP-4 inhibitors; Diabetes mellitus; Heart failure; Prognosis