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

Aim 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. Research design and methods 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. Results 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. Conclusions 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.