title: Dipeptidyl peptidase-4 inhibitors and heart failure: a meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  Recently, the SAVOR TIMI-53 (Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus--Thrombolysis in Myocardial Infarction-53) reported a significant increase in the risk of hospitalizations for heart failure in patients treated with saxagliptin in comparison with placebo. Aim of the present meta-analysis is the systematic collection and synthesis of information on treatment-emergent cases of acute heart failure described in randomized clinical trials with DPP4.
  
  
  RESULTS
  
  
  
  METHODS
  An extensive Medline, Embase, and Cochrane Database search for "vildagliptin", "sitagliptin", "saxagliptin", "alogliptin", "linagliptin", and "dutogliptin" was performed, collecting all randomized clinical trials on humans up to October 1st, 2013. Studies were included if they satisfied the following criteria: i) randomized trials, ii) duration ≥24 weeks; iii) on type 2 diabetes; iv) comparison of DPP4i with placebo or active drugs. The principal outcome was the effect of DPP4i on the incidence of acute heart failure. A total of 84 eligible trials was identified. The overall risk of acute heart failure was higher in patients treated with DPP4i in comparison with those treated with placebo/active comparators (MH-OR: 1.19[1.03; 1.37]; p = 0.015). When trials with non-cardiovascular outcomes were analysed separately no signal of risk was detectable.
  
  
  CONCLUSIONS
  Available data from RCTs suggest that DPP4i could be associated with an increased risk of heart failure, without any clear evidence of differences among drugs of the class. Although it is plausible that the risk is greater in some sub-populations of patients, current evidence is not yet sufficient to identify susceptible patients.
authors.affiliation: Section of Geriatric and Medicine, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Monami
authors.affiliation: Obesity Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy; Diabetes Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Dicembrini
authors.affiliation: Diabetes Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. Electronic address: edoardo.mannucci@unifi.it.
authors.forename: E
authors.initials: E
authors.lastname: Mannucci
mesh_terms: D000208:Acute Disease; D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004151:Dipeptides / Q000009:adverse effects / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D006333:Heart Failure / Q000453:epidemiology* / Q000209:etiology; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; C502994:saxagliptin; D000218:Adamantane
keywords: DPP-4 inhibitors; Heart failure; Meta-analysis