(HealthDay News) — Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are associated with increased risk of gastrointestinal adverse events (AEs), with risk varying based on dose, background medications, and type of GLP-1 RA, according to research published in Diabetes, Obesity and Metabolism.

Karolin Bettge, from St. Josef Hospital in Bochum, Germany, and colleagues conducted a systematic literature review and selected 32 phase 3 clinical trials with GLP-1 RAs. They analyzed the proportion of patients reporting nausea, vomiting, or diarrhea for different doses and glucose-lowering background medications.

The researchers observed a dose-dependent risk for nausea for long-acting agents and across all GLP-1 RAs (P = .0063 and .0017, respectively); a similar trend was seen for vomiting (P = .23). There was a dose-dependent risk for diarrhea (P = .031). More nausea and vomiting were seen for background treatment with metformin (P = .04 and .0009, respectively). Less nausea and less diarrhea were seen for lixisenatide vs exenatide (twice/day). The risk was similar for dulaglutide and liraglutide, while less risk was seen for exenatide and albiglutide vs liraglutide. Compared with short-acting agents, long-acting GLP-1 RAs correlated with less nausea and vomiting but more diarrhea.

“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,” the authors write.

Several authors disclosed financial ties to the pharmaceutical industry.


  1. Bettge K, Kahle M, Abd El Aziz MS, Meier JJ, Nauck MA. Occurrence of nausea, vomiting, and diarrhea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: A systematic analysis of published clinical trials. Diabetes Obes Metab. 2016. doi:10.1111/dom,12824.