title: Cardiovascular Safety of Dipeptidyl-Peptidase IV Inhibitors: A Meta-Analysis of Placebo-Controlled Randomized Trials.
abstract: BACKGROUND
  Large randomized trials have shown conflicting evidence regarding the cardiovascular safety of dipeptidyl-peptidase 4 (DPP-4) inhibitors. Systematic reviews have been limited by incomplete data and inclusion of observational studies. This study aimed to systematically evaluate the cardiovascular safety of DPP-4 inhibitors in patients with type 2 diabetes.
  
  
  METHODS
  Electronic databases were searched for randomized trials that compared DPP-4 inhibitors versus placebo and reported cardiovascular outcomes. The main outcome assessed in this analysis was heart failure. Other outcomes included all-cause mortality, cardiovascular mortality, myocardial infarction, and ischemic stroke. Summary odds ratios (ORs) were primarily constructed using Peto's model.
  
  
  RESULTS
  A total of 90 trials with 66,730 patients were included. Compared with placebo, DPP-4 inhibitors were associated with a non-significant increased risk of heart failure [OR 1.11, 95% confidence interval (CI) 0.99-1.25, P = 0.07] at a mean of 108 weeks. The risk of all-cause mortality (OR 1.03, 95% CI 0.94-1.12, P = 0.53), cardiovascular mortality (OR 1.02, 95% CI 0.92-1.14, P = 0.72), myocardial infarction (OR 0.98, 95% CI 0.88-1.09, P = 0.69), and ischemic stroke (OR 0.99, 95% CI 0.85-1.15, P = 0.92) was similar between both groups.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, the safety profile of DPP-4 inhibitors is similar to placebo. As a class, there is only weak evidence for an increased risk of heart failure.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA. islam.elgendy@medicine.ufl.edu.
authors.forename: Islam Y
authors.initials: IY
authors.lastname: Elgendy
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA.
authors.forename: Ahmed N
authors.initials: AN
authors.lastname: Mahmoud
authors.affiliation: Department of Medicine, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Amr F
authors.initials: AF
authors.lastname: Barakat
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA.
authors.forename: Akram Y
authors.initials: AY
authors.lastname: Elgendy
authors.affiliation: Department of Medicine, University of Arkansas, Little Rock, AR, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Saad
authors.affiliation: Division of Cardiovascular Medicine, Jefferson University Hospital/Christiana Care Health System, Newark, DE, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abuzaid
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA.
authors.forename: Siddarth A
authors.initials: SA
authors.lastname: Wayangankar
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA.|North Florida/South Georgia Veterans Health System, Gainesville, FL, USA.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Bavry
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents