Title of project

Investigating the role of glucose-dependent insulinotropic polypeptide in the regulation of nausea and emesis

Abstract

Gastrointestinal issues such as nausea and vomiting are common side effects of glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) targeting compounds, which are highly effective in treating metabolic diseases like type 2 diabetes and obesity. Despite the therapeutic benefits of the compounds, the side effects can limit patient adherence and the possibility to use higher, more effective doses. Recent findings from animal studies suggest that glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) agonists may alleviate GLP-1R-induced nausea and vomiting.

This proof-of-concept project aims to explore the antiemetic potential of native GIP in humans through two clinical sub-studies. First sub-study will investigate GIP’s antiemetic properties by measuring nausea in healthy individuals following ipecac intake or GLP-1 infusion. Second substudy will assess GIP activity in the human brain by measuring blood oxygen level-dependent (BOLD) signals in the area postrema, a key brain region involved in emesis, using functional magnetic resonance imaging.

If confirmed, GIP’s antiemetic actions could significantly benefit patients undergoing GLP-1 analogue therapy by improving tolerability for higher dosages. Furthermore, GIP may emerge as a broader antiemetic agent for other nausea-inducing treatments, including chemotherapy, pregnancy-related nausea, and infections. This project will provide new insights into GIP’s physiological actions in the central nervous system and its therapeutic potential in managing nausea.