title: Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists.
  
  
  METHODS
  MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration ≥12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events.
  
  
  RESULTS
  Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50-1.08), P = .12 (0.85 (0.50-1.45), P = .55, and 0.69 (0.40-1.22), P = .20, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25-0.83), P = .009, and 1.05 (0.63-1.76), P = .84, respectively.
  
  
  CONCLUSIONS
  To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect.
authors.affiliation: Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, University of Florence and Careggi Teaching Hospital, 50141 Florence, Italy. mmonami@libero.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Monami
authors.forename: Francesco
authors.initials: F
authors.lastname: Cremasco
authors.forename: Caterina
authors.initials: C
authors.lastname: Lamanna
authors.forename: Claudia
authors.initials: C
authors.lastname: Colombi
authors.forename: Carla Maria
authors.initials: CM
authors.lastname: Desideri
authors.forename: Iacopo
authors.initials: I
authors.lastname: Iacomelli
authors.forename: Niccolò
authors.initials: N
authors.lastname: Marchionni
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
mesh_terms: D000465:Algorithms; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069450:Liraglutide; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists*; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C541736:taspoglutide; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide