Journal
EXPERT OPINION ON DRUG DISCOVERY
Volume 18, Issue 6, Pages 659-669Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/17460441.2023.2203911
Keywords
Glucose dependent insulinotropic polypeptide; glucagon like peptide-1; gut hormones; obesity; type 2 diabetes
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With the increasing obesity rates worldwide, there is a critical need for new pharmacotherapies to combat this pandemic. This review focuses on the design of therapeutics targeting the GIPR to facilitate weight loss. The authors highlight the paradoxical finding that both GIPR agonism and antagonism seem to provide metabolic benefits when combined with GLP-1 R agonism, and discuss the therapeutic potential of compounds targeting the GIPR alongside the GLP-1 R and the glucagon receptor.
IntroductionWith obesity rates growing globally, there is a paramount need for new obesity pharmacotherapies to tackle this pandemic.Areas coveredThis review focuses on the design of therapeutics that target the glucose-dependent insulinotropic polypeptide receptor (GIPR) to aid weight loss. The authors highlight the paradoxical observation that both GIPR agonism and antagonism appear to provide metabolic benefits when combined with glucagon-like peptide-1 receptor (GLP-1 R) agonism. The therapeutic potential of compounds that target the GIPR alongside the GLP-1 R and the glucagon receptor are discussed, and the impressive clinical findings of such compounds are reviewed.Expert opinionIn this area, the translation of pre-clinical findings to clinical studies appears to be particularly difficult. Well-designed physiological studies in man are required to answer the paradox highlighted above, and to support the safe future development of a combination of GLP-1 R/GIPR targeting therapies.
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