Effects of GLP-1 and Other Gut Hormone Receptors on the Gastrointestinal Tract and Implications in Clinical Practice

Abstract

Agonists targeting the receptors of incretin hormones, glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, have been well established for the treatment of type 2 diabetes mellitus. There is increasing awareness that gastroenterologists and hepatologists should be treating obesity when patients present to their clinics. In addition, gastroenterologists and hepatologists should be aware of the effects of these classes of medications prescribed by other providers. Therefore, given the widespread use of incretin agonists for obesity treatment and weight loss, it is important to recognize their effects in the gastrointestinal tract, which could constitute significant benefits in weight loss and cardiometabolic benefits, but can be associated with adverse effects that constitute a potential barrier to their use, particularly at higher doses. Multiple studies reviewed in this article document the diverse effects of these drugs on the GLP-1 receptors that are widely expressed in the human body, including the nervous system modulating appetite, the gastrointestinal tract modifying gastric emptying, and lipid metabolism regulation leading to reduction in fat deposition. The objective of this review is to summarize the mechanism of action of incretin receptor agonists, their effects in the gastrointestinal tract, and implications in clinical practice, particularly in the practice of gastroenterology, endoscopy, and surgery.

Effects of Saponins on Lipid Metabolism: The Gut–Liver Axis Plays a Key Role

“…Insulin produced by the pancreas can affect appetite by regulating blood glucose levels and peripheral cell metabolic status and can also cross the blood-brain barrier to inhibit the expression of NPY/AGRP and increase the expression of POMC/CART to achieve the effect of appetite suppression, which is similar to the role of leptin in the hypothalamus [34]. In addition, hormones such as cholecystokinin (CCK), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) have the same effect of increasing satiety and suppressing appetite [35]. Both gastrointestinal and peripheral signaling pathways ultimately act on NPY/AgRP neurons and POMC/CART neurons in the arcuate nucleus of the hypothalamus to regulate appetite through the activation or inhibition of the two, and the multiple factors interact and control each other to form an appetite-regulating network, which jointly regulates appetite.…”

Impact of glucagon-like peptide receptor agonists on endoscopy and its preoperative management: Guidelines, challenges, and future directions

“…Regardless, the recent American Society of Anesthesiologists (ASA) guideline recommends holding GLP-1RAs either on the day of the procedure (for daily dosing) or a week prior to the procedure (for weekly dosing)[ 14 - 16 ]. On the contrary, gastrointestinal societies have recommended individualized approaches when considering endoscopy in this subset of patients[ 17 , 18 ]. In the following editorial, we review the current societal guidelines, clinical practice, and future directions regarding the usage of GLP-1RAs in patients undergoing an endoscopic procedure.…”

Obesity and GI Diseases: A Major Problem Weighing on Our Guts and Minds

“…In keeping with the evolving role of GI specialists as hubs for obesity management, we need knowledge regarding surgical, endoscopic, and medical options. The current issue focuses on the optimal use of these modalities as well as the complications and consequences of obesity management (21)(22)(23). Endoscopic treatments have blurred the lines between surgical and nonsurgical therapies for obesity (24,25).…”