title: Upper and/or lower gastrointestinal adverse events with glucagon-like peptide-1 receptor agonists: Incidence and consequences.
abstract: To characterize gastrointestinal adverse events (AEs) with different glucagon-like peptide-1 receptor agonists (GLP-1RAs).
  
  
  
  Two retrospective intention-to-treat analyses of 6-month patient-level data were conducted. Data from three studies comparing exenatide once weekly (n = 617) with exenatide twice daily (n = 606) were pooled, and one (DURATION-6) comparing exenatide once weekly (n = 461) with liraglutide (n = 450) was analysed separately. Patient-reported gastrointestinal AEs were classified as upper or lower, AE incidences and timing were determined, subgroups were analysed, and associations of gastrointestinal AEs with efficacy were examined.
  
  
  
  Nausea was the most common gastrointestinal AE for all treatments. Fewer exenatide once-weekly-treated vs exenatide twice-daily- or liraglutide-treated patients reported gastrointestinal AEs (34% vs 45% and 25% vs 41%, respectively; both P  < .0001). Fewer exenatide once-weekly-treated patients reported upper plus lower events than liraglutide-treated patients ( P  < .001); the difference between exenatide once weekly and twice daily was not significant. Within each group, more women than men reported gastrointestinal AEs. Events occurrred early and were predominantly mild. Glycated haemoglobin reductions were similar for patients with or without gastrointestinal AEs. Weight loss was greater for patients with gastrointestinal AEs with exenatide once weekly and exenatide twice daily ( P  < .05); no difference was observed in DURATION-6.
  
  
  
  Gastrointestinal AEs were less frequent with exenatide once weekly vs exenatide twice daily or liraglutide, and combined upper and lower events occurred less often. Gastrointestinal AEs were typically mild and occurred early. Gastrointestinal AEs did not affect glycaemic control but may be associated with greater weight loss.
authors.affiliation: Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: Community Clinical Research Center, MedStar Health Research Institute, Hyattsville, Maryland.
authors.forename: Vanita R
authors.initials: VR
authors.lastname: Aroda
authors.affiliation: Pharmapace, San Diego, California.
authors.forename: Jenny
authors.initials: J
authors.lastname: Han
authors.affiliation: Clinical Research, AstraZeneca, Gaithersburg, Maryland.
authors.forename: Elise
authors.initials: E
authors.lastname: Hardy
authors.affiliation: Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Chris K
authors.identifier: 0000-0002-5527-256X
authors.initials: CK
authors.lastname: Rayner
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000517:prevention & control; D015994:Incidence; D054795:Incretins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D057194:Intention to Treat Analysis; D000069450:Liraglutide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D010352:Patient Dropouts; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D057566:Self Report; D012720:Severity of Illness Index; D012737:Sex Factors; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D054795:Incretins; D000069450:Liraglutide; D010455:Peptides; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human
keywords: 
  GLP-1 receptor agonists; adverse events; exenatide; gastrointestinal disorders; liraglutide; type 2 diabetes