Glucagon‐like peptide‐1 in diabetes care: Can glycaemic control be achieved without nausea and vomiting?. (14th September 2021)

• Record Type: Journal Article
• Authors: Borner, Tito; Tinsley, Ian C.; Doyle, Robert P.; Hayes, Matthew R.; De Jonghe, Bart C.
• Is Part Of: British journal of pharmacology. Volume 179:Number 4(2022)
• Page Start: 542
• Page End: 556
• Publication Date: 2021-09-14
• Subjects: area postrema -- cobinamide -- corrination -- diabetes mellitus -- emesis -- GIPR/GLP‐1R dual agonists -- glucose‐dependent insulinotropic polypeptide -- hindbrain -- side effects -- tirzepatide -- vitamin B12; Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.15647
• Languages: English
• ISSNs: 0007-1188

Abstract

Abstract : Introduced less than two decades ago, glucagon‐like peptide‐1 receptor agonists rapidly reshaped the field of Type 2 diabetes mellitus (T2DM) care by providing glycaemic control in tandem with weight loss. However, FDA‐approved GLP‐1 receptor agonists are often accompanied by nausea and emesis and, in some lean T2DM patients, by undesired anorexia. Importantly, the hypophagic and emetic effects of GLP‐1 receptor agonists are caused by activation of central GLP‐1 receptors. This review summarizes two different approaches to mitigate the incidence and severity of nausea and emesis related to GLP‐1 receptor agonists: conjugation with vitamin B12, or related corrin ring‐containing compounds ('corrination'), and development of dual agonists of GLP‐1 receptors with glucose‐dependent insulinotropic polypeptide (GIP). Such approaches could lead to the generation of GLP‐1 receptor agonists with improved therapeutic efficacy, thus decreasing treatment attrition, increasing patient compliance and extending treatment to a broader population of T2DM patients. The data reviewed show that it is possible to pharmacologically separate the emetic effects of GLP‐1 receptor agonists from their glucoregulatory action. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc