title: Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate.
  
  
  RESULTS
  In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was -0.66% [six studies; 95% confidence interval (CI) -1.14 to -0.19; I(2)  = 88%] with albiglutide, and -1.18% (seven studies; 95% CI -1.34 to -1.02; I(2)  = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences -0.40%; 95% CI -0.66 to -0.14; I(2)  = 85%, -0.44%; 95% CI -0.58 to -0.29; I(2)  = 40% and -0.28; 95% CI -0.45 to -0.10; I(2)  = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions.
  
  
  CONCLUSIONS
  Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: T
authors.initials: T
authors.lastname: Karagiannis
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-3261-2979
authors.initials: A
authors.lastname: Liakos
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Bekiari
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Athanasiadou
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Paschos
authors.affiliation: Third Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Vasilakou
authors.affiliation: Division of Preventive, Occupational, and Aerospace Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mainou
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Rika
authors.affiliation: Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Boura
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK.|Harris Manchester College, University of Oxford, Oxford, UK.
authors.forename: D R
authors.initials: DR
authors.lastname: Matthews
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.|Harris Manchester College, University of Oxford, Oxford, UK.
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-0221-4072
authors.initials: A
authors.lastname: Tsapas
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000819:agonists* / Q000031:analogs & derivatives; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000031:analogs & derivatives; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage; D054795:Incretins / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D014688:Venoms / Q000008:administration & dosage
chemical_list: D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D054795:Incretins; D008687:Metformin; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014688:Venoms; C517652:hemoglobin A1c protein, human; C534611:rGLP-1 protein; C555680:dulaglutide
keywords: GLP-1; GLP-1 analogue; incretin therapy; meta-analysis; type 2 diabetes