Gastrointestinal effects of incretin hormone receptor agonists

Agonists of incretin receptors (AIRs), such as glucagon‑like peptide‑1 (GLP‑1) and glucose‑dependent insulinotropic peptide (GIP), are widely used in the complex treatment of type 2 diabetes mellitus (T2DM) and obesity worldwide. To date, there are 7 AIRs approved by the FDA and available for clinical use. The effect of these drugs on the gastrointestinal tract (GI) and the liver is significant and has significance in the clinical practice of gastroenterology and hepatology. Widespread use of this class of drugs has shown that, while effective in treating T2DM, obesity, and metabolic‑associated steatotic liver disease (MASLD), they also have undesirable side effects, most often gastrointestinal, such as nausea, vomiting, diarrhea, and constipation. These side effects, commonly associated with delayed gastric emptying, may decrease their significant benefits in the treatment of T2DM, reduce body weight and improve cardiometabolic status, and may become a barrier to their use at higher doses. In many studies, these side effects are dose‑dependent, most of them are observed during dose escalation, and they tend to improve with continued use, although the mechanisms of this improvement are still unclear. Recent concerns also relate to the risks of using GLP‑1 receptor agonists in perioperative patient management, given that increased residual gastric content in patients treated with ARI increases the risk of aspiration in these patients. Therefore, when using short‑acting ARIs, it is not recommended to take them on the day of surgery, and when using long‑acting drugs, discontinue their use at least 7 days before surgery, or even earlier if necessary. Many other ARIs are expected to be approved soon and will enter the therapeutic armamentarium.