Search Results
Search for other papers by Ryan A Lafferty in
Google Scholar
PubMed
Search for other papers by Peter R Flatt in
Google Scholar
PubMed
Search for other papers by Victor A Gault in
Google Scholar
PubMed
Search for other papers by Nigel Irwin in
Google Scholar
PubMed
Recent approval of the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, tirzepatide, for the management of type 2 diabetes mellitus (T2DM) has reinvigorated interest in exploitation of GIP receptor (GIPR) pathways as a means of metabolic disease management. However, debate has long surrounded the use of the GIPR as a therapeutic target and whether agonism or antagonism is of most benefit in management of obesity/diabetes. This controversy appears to be partly resolved by the success of tirzepatide. However, emerging studies indicate that prolonged GIPR agonism may desensitise the GIPR to essentially induce receptor antagonism, with this phenomenon suggested to be more pronounced in the human than rodent setting. Thus, deliberation continues to rage in relation to benefits of GIPR agonism vs antagonism. That said, as with GIPR agonism, it is clear that the metabolic advantages of sustained GIPR antagonism in obesity and obesity-driven forms of diabetes can be enhanced by concurrent GLP-1 receptor (GLP-1R) activation. This narrative review discusses various approaches of pharmacological GIPR antagonism including small molecule, peptide, monoclonal antibody and peptide-antibody conjugates, indicating stage of development and significance to the field. Taken together, there is little doubt that interesting times lie ahead for GIPR agonism and antagonism, either alone or when combined with GLP-1R agonists, as a therapeutic intervention for the management of obesity and associated metabolic disease.
Search for other papers by Ken K Y Ho in
Google Scholar
PubMed
combining risk identification, lifestyle and therapeutic intervention. In the area of obesity, the energy homeostatic regulating pathways will have been elucidated, with ligands and receptors identified. A polypharmacy approach will combine the use of anti
Search for other papers by Pegah JafariNasabian in
Google Scholar
PubMed
Search for other papers by Julia E Inglis in
Google Scholar
PubMed
Search for other papers by Wendimere Reilly in
Google Scholar
PubMed
Search for other papers by Owen J Kelly in
Google Scholar
PubMed
Search for other papers by Jasminka Z Ilich in
Google Scholar
PubMed
deficiencies ( Pray et al. 2010 ). Another major issue interfering with nutrient absorption and/or intake in elderly is the use of multiple medications, known as polypharmacy. For example, research on proton pump inhibitors (PPI) and H 2 blockers, the
Search for other papers by Bernard Khoo in
Google Scholar
PubMed
Search for other papers by Tricia Mei-Mei Tan in
Google Scholar
PubMed
Unimolecular polypharmacy for treatment of diabetes and obesity . Cell Metabolism 24 51 – 62 . ( https://doi.org/10.1016/j.cmet.2016.06.021 ) Wadden TA Hollander P Klein S Niswender K Woo V Hale PM Aronne L & NN8022-1923 Investigators
Search for other papers by Jonathan D Douros in
Google Scholar
PubMed
Search for other papers by Jacek Mokrosinski in
Google Scholar
PubMed
Search for other papers by Brian Finan in
Google Scholar
PubMed
TD & DiMarchi RD 2016 Unimolecular polypharmacy for treatment of diabetes and obesity . Cell Metabolism 24 51 – 62 . ( https://doi.org/10.1016/j.cmet.2016.06.021 ) van der Lee MM Verkaar F Wat JW van Offenbeek J Timmerman M Voorneveld
