Glucose-dependent insulinotropic polypeptide (GIP)

Timo D Müller; Alice Adriaenssens; Bo Ahrén; Matthias Blüher; Andreas L Birkenfeld; Jonathan E Campbell; Matthew P Coghlan; David D'Alessio; Carolyn F Deacon; Stefano DelPrato; Jonathan D Douros; Daniel J Drucker; Natalie S Figueredo Burgos; Peter R Flatt; Brian Finan; Ruth E Gimeno; Fiona M Gribble; Matthew R Hayes; Christian Hölscher; Jens J Holst; Patrick J Knerr; Filip K Knop; Christine M Kusminski; Arkadiusz Liskiewicz; Guillaume Mabilleau; Stephanie A Mowery; Michael A Nauck; Aaron Novikoff; Frank Reimann; Anna G Roberts; Mette M Rosenkilde; Ricardo J Samms; Philip E Scherer; Randy J Seeley; Kyle W Sloop; Christian Wolfrum; Denise Wootten; Richard D DiMarchi; Matthias H Tschöp

doi:10.1016/j.molmet.2025.102118

Glucose-dependent insulinotropic polypeptide (GIP)

Timo D Müller
, Alice Adriaenssens
, Bo Ahrén
, Matthias Blüher
, Andreas L Birkenfeld
, Jonathan E Campbell
, Matthew P Coghlan
, David D'Alessio
, Carolyn F Deacon
, Stefano DelPrato
, Jonathan D Douros
, Daniel J Drucker
, Natalie S Figueredo Burgos
, Peter R Flatt
, Brian Finan
, Ruth E Gimeno
, Fiona M Gribble
, Matthew R Hayes
, Christian Hölscher
, Jens J Holst

Patrick J Knerr, Filip K Knop, Christine M Kusminski, Arkadiusz Liskiewicz, Guillaume Mabilleau, Stephanie A Mowery, Michael A Nauck, Aaron Novikoff, Frank Reimann, Anna G Roberts, Mette M Rosenkilde, Ricardo J Samms, Philip E Scherer, Randy J Seeley, Kyle W Sloop, Christian Wolfrum, Denise Wootten, Richard D DiMarchi, Matthias H Tschöp

Research output: Contribution to journal › Review article › peer-review

49 Citations (Scopus)

335 Downloads (Pure)

Abstract

BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in the maintenance of glucose tolerance in healthy humans. Until recently GIP had not been developed as a therapeutic and thus has been overshadowed by the other incretin, glucagon-like peptide 1 (GLP-1), which is the basis for several successful drugs to treat diabetes and obesity. However, there has been a rekindling of interest in GIP biology in recent years, in great part due to pharmacology demonstrating that both GIPR agonism and antagonism may be beneficial in treating obesity and diabetes. This apparent paradox has reinvigorated the field, led to new lines of investigation, and deeper understanding of GIP.

SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GIP biology and discuss the therapeutic implications of GIPR signal modification on various diseases.

MAJOR CONCLUSIONS: Following its classification as an incretin hormone, GIP has emerged as a pleiotropic hormone with a variety of metabolic effects outside the endocrine pancreas. The numerous beneficial effects of GIPR signal modification render the peptide an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, drug-induced nausea and both bone and neurodegenerative disorders.

Original language	English
Article number	102118
Pages (from-to)	1-67
Number of pages	67
Journal	Molecular metabolism
Volume	95
Early online date	28 Feb 2025
DOIs	https://doi.org/10.1016/j.molmet.2025.102118
Publication status	Published (in print/issue) - 31 May 2025

Bibliographical note

Data Availability Statement

No data was used for the research described in the article

Funding

This work was funded by the European Union within the scope or the European Research Council ERC-CoG Trusted no.101044445, awarded to TDM.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Diabetes
GLP-1
GIP
Incretin
Insulin
Obesity

Access to Document

10.1016/j.molmet.2025.102118Licence: CC BY

1-s2.0-S2212877825000250-mainFinal published version, 7.52 MBLicence: CC BY

Cite this

Müller, T. D., Adriaenssens, A., Ahrén, B., Blüher, M., Birkenfeld, A. L., Campbell, J. E., Coghlan, M. P., D'Alessio, D., Deacon, C. F., DelPrato, S., Douros, J. D., Drucker, D. J., Figueredo Burgos, N. S., Flatt, P. R., Finan, B., Gimeno, R. E., Gribble, F. M., Hayes, M. R., Hölscher, C., ... Tschöp, M. H. (2025). Glucose-dependent insulinotropic polypeptide (GIP). Molecular metabolism, 95, 1-67. Article 102118. https://doi.org/10.1016/j.molmet.2025.102118

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title = "Glucose-dependent insulinotropic polypeptide (GIP)",

abstract = "BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in the maintenance of glucose tolerance in healthy humans. Until recently GIP had not been developed as a therapeutic and thus has been overshadowed by the other incretin, glucagon-like peptide 1 (GLP-1), which is the basis for several successful drugs to treat diabetes and obesity. However, there has been a rekindling of interest in GIP biology in recent years, in great part due to pharmacology demonstrating that both GIPR agonism and antagonism may be beneficial in treating obesity and diabetes. This apparent paradox has reinvigorated the field, led to new lines of investigation, and deeper understanding of GIP.SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GIP biology and discuss the therapeutic implications of GIPR signal modification on various diseases.MAJOR CONCLUSIONS: Following its classification as an incretin hormone, GIP has emerged as a pleiotropic hormone with a variety of metabolic effects outside the endocrine pancreas. The numerous beneficial effects of GIPR signal modification render the peptide an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, drug-induced nausea and both bone and neurodegenerative disorders.",

keywords = "Diabetes, GLP-1, GIP, Incretin, Insulin, Obesity",

author = "M{\"u}ller, \{Timo D\} and Alice Adriaenssens and Bo Ahr{\'e}n and Matthias Bl{\"u}her and Birkenfeld, \{Andreas L\} and Campbell, \{Jonathan E\} and Coghlan, \{Matthew P\} and David D'Alessio and Deacon, \{Carolyn F\} and Stefano DelPrato and Douros, \{Jonathan D\} and Drucker, \{Daniel J\} and \{Figueredo Burgos\}, \{Natalie S\} and Flatt, \{Peter R\} and Brian Finan and Gimeno, \{Ruth E\} and Gribble, \{Fiona M\} and Hayes, \{Matthew R\} and Christian H{\"o}lscher and Holst, \{Jens J\} and Knerr, \{Patrick J\} and Knop, \{Filip K\} and Kusminski, \{Christine M\} and Arkadiusz Liskiewicz and Guillaume Mabilleau and Mowery, \{Stephanie A\} and Nauck, \{Michael A\} and Aaron Novikoff and Frank Reimann and Roberts, \{Anna G\} and Rosenkilde, \{Mette M\} and Samms, \{Ricardo J\} and Scherer, \{Philip E\} and Seeley, \{Randy J\} and Sloop, \{Kyle W\} and Christian Wolfrum and Denise Wootten and DiMarchi, \{Richard D\} and Tsch{\"o}p, \{Matthias H\}",

year = "2025",

month = may,

day = "31",

doi = "10.1016/j.molmet.2025.102118",

language = "English",

volume = "95",

pages = "1--67",

journal = "Molecular metabolism",

issn = "2212-8778",

publisher = "Elsevier GmbH",

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Müller, TD, Adriaenssens, A, Ahrén, B, Blüher, M, Birkenfeld, AL, Campbell, JE, Coghlan, MP, D'Alessio, D, Deacon, CF, DelPrato, S, Douros, JD, Drucker, DJ, Figueredo Burgos, NS, Flatt, PR, Finan, B, Gimeno, RE, Gribble, FM, Hayes, MR, Hölscher, C, Holst, JJ, Knerr, PJ, Knop, FK, Kusminski, CM, Liskiewicz, A, Mabilleau, G, Mowery, SA, Nauck, MA, Novikoff, A, Reimann, F, Roberts, AG, Rosenkilde, MM, Samms, RJ, Scherer, PE, Seeley, RJ, Sloop, KW, Wolfrum, C, Wootten, D, DiMarchi, RD & Tschöp, MH 2025, 'Glucose-dependent insulinotropic polypeptide (GIP)', Molecular metabolism, vol. 95, 102118, pp. 1-67. https://doi.org/10.1016/j.molmet.2025.102118

TY - JOUR

T1 - Glucose-dependent insulinotropic polypeptide (GIP)

AU - Müller, Timo D

AU - Adriaenssens, Alice

AU - Ahrén, Bo

AU - Blüher, Matthias

AU - Birkenfeld, Andreas L

AU - Campbell, Jonathan E

AU - Coghlan, Matthew P

AU - D'Alessio, David

AU - Deacon, Carolyn F

AU - DelPrato, Stefano

AU - Douros, Jonathan D

AU - Drucker, Daniel J

AU - Figueredo Burgos, Natalie S

AU - Flatt, Peter R

AU - Finan, Brian

AU - Gimeno, Ruth E

AU - Gribble, Fiona M

AU - Hayes, Matthew R

AU - Hölscher, Christian

AU - Holst, Jens J

AU - Knerr, Patrick J

AU - Knop, Filip K

AU - Kusminski, Christine M

AU - Liskiewicz, Arkadiusz

AU - Mabilleau, Guillaume

AU - Mowery, Stephanie A

AU - Nauck, Michael A

AU - Novikoff, Aaron

AU - Reimann, Frank

AU - Roberts, Anna G

AU - Rosenkilde, Mette M

AU - Samms, Ricardo J

AU - Scherer, Philip E

AU - Seeley, Randy J

AU - Sloop, Kyle W

AU - Wolfrum, Christian

AU - Wootten, Denise

AU - DiMarchi, Richard D

AU - Tschöp, Matthias H

PY - 2025/5/31

Y1 - 2025/5/31

N2 - BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in the maintenance of glucose tolerance in healthy humans. Until recently GIP had not been developed as a therapeutic and thus has been overshadowed by the other incretin, glucagon-like peptide 1 (GLP-1), which is the basis for several successful drugs to treat diabetes and obesity. However, there has been a rekindling of interest in GIP biology in recent years, in great part due to pharmacology demonstrating that both GIPR agonism and antagonism may be beneficial in treating obesity and diabetes. This apparent paradox has reinvigorated the field, led to new lines of investigation, and deeper understanding of GIP.SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GIP biology and discuss the therapeutic implications of GIPR signal modification on various diseases.MAJOR CONCLUSIONS: Following its classification as an incretin hormone, GIP has emerged as a pleiotropic hormone with a variety of metabolic effects outside the endocrine pancreas. The numerous beneficial effects of GIPR signal modification render the peptide an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, drug-induced nausea and both bone and neurodegenerative disorders.

AB - BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in the maintenance of glucose tolerance in healthy humans. Until recently GIP had not been developed as a therapeutic and thus has been overshadowed by the other incretin, glucagon-like peptide 1 (GLP-1), which is the basis for several successful drugs to treat diabetes and obesity. However, there has been a rekindling of interest in GIP biology in recent years, in great part due to pharmacology demonstrating that both GIPR agonism and antagonism may be beneficial in treating obesity and diabetes. This apparent paradox has reinvigorated the field, led to new lines of investigation, and deeper understanding of GIP.SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GIP biology and discuss the therapeutic implications of GIPR signal modification on various diseases.MAJOR CONCLUSIONS: Following its classification as an incretin hormone, GIP has emerged as a pleiotropic hormone with a variety of metabolic effects outside the endocrine pancreas. The numerous beneficial effects of GIPR signal modification render the peptide an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, drug-induced nausea and both bone and neurodegenerative disorders.

KW - Diabetes

KW - GLP-1

KW - GIP

KW - Incretin

KW - Insulin

KW - Obesity

UR - https://www.sciencedirect.com/science/article/pii/S2212877825000250?via%3Dihub

UR - https://www.scopus.com/pages/publications/86000367480

U2 - 10.1016/j.molmet.2025.102118

DO - 10.1016/j.molmet.2025.102118

M3 - Review article

C2 - 40024571

SN - 2212-8778

VL - 95

SP - 1

EP - 67

JO - Molecular metabolism

JF - Molecular metabolism

M1 - 102118

ER -

Glucose-dependent insulinotropic polypeptide (GIP)

Abstract

Bibliographical note

Data Availability Statement

Funding

UN SDGs

Keywords

Access to Document

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Cite this