title: Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: A systematic analysis of published clinical trials.
abstract: GLP-1 receptor agonists (RAs) may cause nausea, vomiting or diarrhoea. The aim of this study was to assess the risk of adverse events (AEs) with GLP-1 RAs and their relation to dose, background medication and duration of action.
  
  
  
  The PubMed database was searched and 32 clinical trials with GLP-1 RAs (phase 3) were selected. We performed a systematic analysis and compared the proportion of patients reporting nausea, vomiting or diarrhoea, for different doses and glucose-lowering background medications, and relative to a reference compound within the subclasses of short- (exenatide b.i.d.) and long-acting (liraglutide) GLP-1 RAs, calculating the relative risks ± 95% confidence intervals.
  
  
  
  The risk of nausea was dose-dependent for long-acting (P = .0063) and across all GLP-1 RAs (P = .0017), and a similar trend was observed for vomiting (P = .23). Diarrhoea was dose-dependent (P = .031). Background treatment with metformin was associated with more nausea (P = .04) and vomiting (P = .0009). Compared to exenatide b.i.d., there was less nausea and diarrhoea with lixisenatide. Compared to liraglutide, there was a similar risk associated with dulaglutide, and less with exenatide q.w. and albiglutide. Long-acting GLP-1 RAs were associated with less nausea and vomiting, but with more diarrhoea than short-acting agents.
  
  
  
  GLP-1 RAs are associated with gastrointestinal AEs that are related to dose and background medications (especially metformin) and may vary in a compound-specific manner. Long-acting agents are associated with less nausea and vomiting but with more diarrhoea.
authors.affiliation: Division of Diabetology, Medical Department I, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Bettge
authors.affiliation: Division of Diabetology, Medical Department I, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kahle
authors.affiliation: Division of Diabetology, Medical Department I, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Mirna S
authors.initials: MS
authors.lastname: Abd El Aziz
authors.affiliation: Division of Diabetology, Medical Department I, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.affiliation: Division of Diabetology, Medical Department I, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
mesh_terms: D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced*; D004359:Drug Therapy, Combination; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D000069450:Liraglutide / Q000009:adverse effects*; D008687:Metformin / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced*; D010455:Peptides / Q000009:adverse effects*; D014688:Venoms / Q000009:adverse effects*; D014839:Vomiting / Q000139:chemically induced*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000069450:Liraglutide; D008687:Metformin; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: 
  GLP-1 analogues; 
  GLP-1 receptor agonists; gastrointestinal adverse events; incretin mimetics; side effects