The evolution of the therapeutic concept ‘GIP receptor antagonism’
Glucose-dependent insulinotropic polypeptide (GIP) is an intestinal hormone that potentiates glucose-induced insulin secretion in the postprandial state. GIP exerts a broad range of other physiological actions e.g. in the pancreas, bone tissue, and vasculature. In more than 20 years, GIP receptor an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1570603/full |
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| author | Frederikke Koefoed-Hansen Frederikke Koefoed-Hansen Mads Marstrand Helsted Hüsün Sheyma Kizilkaya Asger Bach Lund Asger Bach Lund Asger Bach Lund Mette Marie Rosenkilde Lærke Smidt Gasbjerg Lærke Smidt Gasbjerg |
| author_facet | Frederikke Koefoed-Hansen Frederikke Koefoed-Hansen Mads Marstrand Helsted Hüsün Sheyma Kizilkaya Asger Bach Lund Asger Bach Lund Asger Bach Lund Mette Marie Rosenkilde Lærke Smidt Gasbjerg Lærke Smidt Gasbjerg |
| author_sort | Frederikke Koefoed-Hansen |
| collection | DOAJ |
| description | Glucose-dependent insulinotropic polypeptide (GIP) is an intestinal hormone that potentiates glucose-induced insulin secretion in the postprandial state. GIP exerts a broad range of other physiological actions e.g. in the pancreas, bone tissue, and vasculature. In more than 20 years, GIP receptor antagonism has contributed to the discoveries of the role of GIP within both human and animal physiology. In 1986, a fragment of the biological active bovine GIP(1-42), was discovered and characterized as the first GIP receptor antagonist. Several different molecules have been identified, including peptides, vaccines against GIP, GIP antibodies, and antibodies against the GIP receptor. Today, GIP receptor antagonists are not only used as scientific tools but due to significant metabolic effects, they also have a therapeutic purpose. The beneficial clinical effects of GIP receptor antagonism are supported by comparable phenotypic traits of individuals with loss-of-function genetic receptor variants. Novel insights into GIP receptor targeting treatment reveal that both GIP receptor antagonists and agonists, when combined with glucagon like peptide 1 (GLP-1) receptor activation, are associated with improved glycemic control and weight loss. This paradoxical scenario highlights the complexity of GIP receptor pharmacology. Moreover, the long-term effects of therapeutic GIP receptor antagonism in humans are not fully elucidated and are thought to depend on the specific drug molecule, receptor functions, and the extent of GLP-1 receptor activation. With this review, we provide an overview of the preclinical and clinical evidence of GIP receptor antagonism from the central early findings to the current therapeutics in clinical development. Finally, the current therapeutic developments and the further therapeutic potential within GIP receptor antagonism are discussed. |
| format | Article |
| id | doaj-art-547ddfea5e0c4ba0a1f4dd0352741b0f |
| institution | DOAJ |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-547ddfea5e0c4ba0a1f4dd0352741b0f2025-08-20T03:13:39ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-05-011610.3389/fendo.2025.15706031570603The evolution of the therapeutic concept ‘GIP receptor antagonism’Frederikke Koefoed-Hansen0Frederikke Koefoed-Hansen1Mads Marstrand Helsted2Hüsün Sheyma Kizilkaya3Asger Bach Lund4Asger Bach Lund5Asger Bach Lund6Mette Marie Rosenkilde7Lærke Smidt Gasbjerg8Lærke Smidt Gasbjerg9Center for Clinical Metabolic Research, Gentofte Hospital, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCenter for Clinical Metabolic Research, Gentofte Hospital, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCenter for Clinical Metabolic Research, Gentofte Hospital, Hellerup, DenmarkDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkClinical Research, Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCenter for Clinical Metabolic Research, Gentofte Hospital, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkGlucose-dependent insulinotropic polypeptide (GIP) is an intestinal hormone that potentiates glucose-induced insulin secretion in the postprandial state. GIP exerts a broad range of other physiological actions e.g. in the pancreas, bone tissue, and vasculature. In more than 20 years, GIP receptor antagonism has contributed to the discoveries of the role of GIP within both human and animal physiology. In 1986, a fragment of the biological active bovine GIP(1-42), was discovered and characterized as the first GIP receptor antagonist. Several different molecules have been identified, including peptides, vaccines against GIP, GIP antibodies, and antibodies against the GIP receptor. Today, GIP receptor antagonists are not only used as scientific tools but due to significant metabolic effects, they also have a therapeutic purpose. The beneficial clinical effects of GIP receptor antagonism are supported by comparable phenotypic traits of individuals with loss-of-function genetic receptor variants. Novel insights into GIP receptor targeting treatment reveal that both GIP receptor antagonists and agonists, when combined with glucagon like peptide 1 (GLP-1) receptor activation, are associated with improved glycemic control and weight loss. This paradoxical scenario highlights the complexity of GIP receptor pharmacology. Moreover, the long-term effects of therapeutic GIP receptor antagonism in humans are not fully elucidated and are thought to depend on the specific drug molecule, receptor functions, and the extent of GLP-1 receptor activation. With this review, we provide an overview of the preclinical and clinical evidence of GIP receptor antagonism from the central early findings to the current therapeutics in clinical development. Finally, the current therapeutic developments and the further therapeutic potential within GIP receptor antagonism are discussed.https://www.frontiersin.org/articles/10.3389/fendo.2025.1570603/fullGIP -glucose-dependent insulinotropic polypeptideantagonismobesitydiabetespharmacology |
| spellingShingle | Frederikke Koefoed-Hansen Frederikke Koefoed-Hansen Mads Marstrand Helsted Hüsün Sheyma Kizilkaya Asger Bach Lund Asger Bach Lund Asger Bach Lund Mette Marie Rosenkilde Lærke Smidt Gasbjerg Lærke Smidt Gasbjerg The evolution of the therapeutic concept ‘GIP receptor antagonism’ Frontiers in Endocrinology GIP -glucose-dependent insulinotropic polypeptide antagonism obesity diabetes pharmacology |
| title | The evolution of the therapeutic concept ‘GIP receptor antagonism’ |
| title_full | The evolution of the therapeutic concept ‘GIP receptor antagonism’ |
| title_fullStr | The evolution of the therapeutic concept ‘GIP receptor antagonism’ |
| title_full_unstemmed | The evolution of the therapeutic concept ‘GIP receptor antagonism’ |
| title_short | The evolution of the therapeutic concept ‘GIP receptor antagonism’ |
| title_sort | evolution of the therapeutic concept gip receptor antagonism |
| topic | GIP -glucose-dependent insulinotropic polypeptide antagonism obesity diabetes pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1570603/full |
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