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Dual and triple incretin-based co-agonists: Novel therapeutics for obesity and diabetes.
Diabetes Ther. 15, 1069-1084 (2024)
The discovery of long-acting incretin receptor agonists represents a major stride forward in tackling the dual epidemic of obesity and diabetes. Here we outline the evolution of incretin-based pharmacotherapy, from exendin-4 to the discovery of the multi-incretin hormone receptor agonists that look set to be our next step toward curing diabetes and obesity. We discuss the multiagonists currently in clinical trials and the improvement in efficacy each new generation of these drugs bring. The success of these agents in preclinical models and clinical trials suggests a promising future for multiagonists in the treatment of metabolic diseases, with the most recent glucose-dependent insulinotropic peptide receptor:glucagon-like peptide 1 receptor:glucagon receptor (GIPR:GLP-1R:GCGR) triagonists rivaling the efficacy of bariatric surgery. However, further research is needed to fully understand how these therapies exert their effect on body weight and in the last section we cover open questions about the potential mechanisms of multiagonist drugs, and the understanding of how gut-brain communication can be leveraged to achieve sustained body weight loss without adverse effects.
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Publication type
Article: Journal article
Document type
Review
Keywords
Diabetes ; Dual-agonist ; Gip ; Glp-1 ; Glucagon ; Incretin ; Obesity ; Triagonist; Dependent Insulinotropic Polypeptide; Glucagon-like Peptide-1; Gastric-inhibitory Polypeptide; Receptor Agonist; Double-blind; Glycemic Control; Cardiovascular Outcomes; Exenatide Exendin-4; Recombinant Leptin; Lipoprotein-lipase
ISSN (print) / ISBN
1869-6961
e-ISSN
1869-6953
Journal
Diabetes Therapy
Quellenangaben
Volume: 15,
Issue: 5,
Pages: 1069-1084
Publisher
Springer
Publishing Place
New York, NY [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Obesity (IDO)
Grants
European Research Council