Designer GLP1 poly-agonist peptides in the management of diabesity. Issue 3 (4th May 2023)

• Record Type: Journal Article
• Authors: Statham, Laura; Pelling, Melina; Hanson, Petra; Kyrou, Ioannis; Randeva, Harpal; Barber, Thomas M
• Is Part Of: Expert review of endocrinology & metabolism. Volume 18:Issue 3(2023)
• Page Start: 231
• Page End: 240
• Publication Date: 2023-05-04
• Subjects: Incretin -- Diabesity -- Glucagon Like Peptide 1 -- obesity -- diabetes; Endocrinology -- Periodicals; Metabolism -- Periodicals; 616.4
• DOI: 10.1080/17446651.2023.2204976
• Languages: English
• ISSNs: 1744-6651

Abstract

ABSTRACT: Introduction: To date, the 21 st Century has witnessed key developments in the management of diabesity (a conflation of obesity and Type 2 Diabetes Mellitus [T2D]), including Glucagon Like Peptide 1 (GLP1) receptor agonist therapies, and recently the 'designer' GLP1 Poly-agonist Peptides (GLP1PPs). Areas covered: A PubMed search of published data on the GLP1PP class of therapies was conducted. The gut-brain axis forms complex multi-directional interlinks that include autonomic nervous signaling, components of the gut microbiota (including metabolic by-products and gram-negative cell wall components [e.g. endotoxinaemia]), and incretin hormones that are secreted from the gut in response to the ingestion of nutrients. The development of dual-incretin agonist therapies includes combinations of the GLP1 peptide with Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (Gcg), Cholecystokinin (CCK), Peptide YY (PYY), and Glucagon-Like Peptide 2 (GLP2). Triple incretin agonist therapies are also under development. Expert opinion: At the dawn of a new era in the therapeutic management of diabesity, the designer GLP1PP class holds great promise, with each novel combination building on a preexisting palimpsest of clinical data and insights. Future innovations of the GLP1PP class will likely enable medically induced weight loss and glycemic control in diabesity to rival or even out-perform those resulting from bariatric surgery.