The antiemetic actions of GIP receptor agonism

Am J Physiol Endocrinol Metab. 2024 Apr 1;326(4):E528-E536. doi: 10.1152/ajpendo.00330.2023. Epub 2024 Mar 13.

Abstract

Nausea and vomiting are primitive aspects of mammalian physiology and behavior that ensure survival. Unfortunately, both are ubiquitously present side effects of drug treatments for many chronic diseases with negative consequences on pharmacotherapy tolerance, quality of life, and prognosis. One of the most critical clinical examples is the profound emesis and nausea that occur in patients undergoing chemotherapy, which continue to be among the most distressing side effects, even with the use of modern antiemetic medications. Similarly, antiobesity/diabetes medications that target the glucagon-like peptide-1 system, despite their remarkable metabolic success, also cause nausea and vomiting in a significant number of patients. These side effects hinder the ability to administer higher dosages for optimal glycemic and weight management and represent the major reasons for treatment discontinuation. Our inability to effectively control these side effects highlights the need to anatomically, molecularly, and functionally characterize novel neural substrates that drive and inhibit nausea and emesis. Here, we discuss clinical and preclinical evidence that highlights the glucose-dependent insulinotropic peptide receptor system as a novel therapeutic central target for the management of nausea and emesis.

Keywords: antiemetic; emesis; gastric inhibitory peptide; glucose-dependent insulinotropic polypeptide; nausea.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiemetics* / adverse effects
  • Humans
  • Mammals
  • Nausea / chemically induced
  • Nausea / drug therapy
  • Quality of Life
  • Receptors, Gastrointestinal Hormone*
  • Vomiting / chemically induced
  • Vomiting / drug therapy

Substances

  • Antiemetics
  • gastric inhibitory polypeptide receptor
  • Receptors, Gastrointestinal Hormone