The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs DOI Open Access
Jonathan D. Douros,

Stephanie A. Mowery,

Patrick J. Knerr

и другие.

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(11), С. 3812 - 3812

Опубликована: Май 29, 2025

Emerging clinical data support the paradoxical notion that glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) agonism and antagonism can provide additive weight loss when combined with a glucagon-like peptide 1 (GLP-1) (GLP-1R) agonist. In this review, we examine motivated initiation of these seemingly contradictory drug discovery programs. We focus on physiologic role GIP in humans, human genetics evidence, rodent genetic models, preclinical non-human primate pharmacology studies. Furthermore, highlight where early findings translated into relevant efficacy development tirzepatide maridebart cafraglutide (MariTide).

Язык: Английский

Glucose-dependent insulinotropic polypeptide (GIP) DOI Creative Commons
Timo D. Müller, Alice E. Adriaenssens,

Bo Ahrén

и другие.

Molecular Metabolism, Год журнала: 2025, Номер 95, С. 102118 - 102118

Опубликована: Фев. 28, 2025

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

Язык: Английский

Процитировано

4

GIPR-Ab/GLP-1 peptide–antibody conjugate requires brain GIPR and GLP-1R for additive weight loss in obese mice DOI Creative Commons

Clarissa M. Liu,

Elizabeth A. Killion, Rola Hammoud

и другие.

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 29, 2025

Язык: Английский

Процитировано

3

GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice DOI Creative Commons
Robert M. Gutgesell, Ahmed Khalil, Arkadiusz Liśkiewicz

и другие.

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 29, 2025

Язык: Английский

Процитировано

3

The role of GIPR in food intake control DOI Creative Commons

Paula-Peace James-Okoro,

Jo E. Lewis, Fiona M. Gribble

и другие.

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Март 17, 2025

Glucose-dependent insulinotropic polypeptide (GIP) is one of two incretin hormones playing key roles in the control food intake, nutrient assimilation, insulin secretion and whole-body metabolism. Recent pharmacological advances clinical trials show that unimolecular co-agonists target receptors for incretins - GIP glucagon-like peptide 1 (GLP-1) offer more effective treatment strategies obesity type 2 diabetes mellitus (T2D) compared with GLP-1 receptor (GLP1R) agonists alone, suggesting previously underappreciated regulating intake body weight. The mechanisms by which regulates energy balance remain controversial as both agonism antagonism (GIPR) produce weight loss improve metabolic outcomes preclinical models. studies have shown GIPR signalling central nervous system (CNS), especially regions brain regulate balance, essential its action on appetite regulation. This finding has sparked interest understanding engages circuits to reduce In this review, we present knowledge around actions regulation potential GIPR/GLP1R may balance.

Язык: Английский

Процитировано

0

Unravelling the GIPR agonist versus antagonist paradox DOI
Alice E. Adriaenssens

Nature Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 29, 2025

Язык: Английский

Процитировано

0

The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs DOI Open Access
Jonathan D. Douros,

Stephanie A. Mowery,

Patrick J. Knerr

и другие.

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(11), С. 3812 - 3812

Опубликована: Май 29, 2025

Emerging clinical data support the paradoxical notion that glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) agonism and antagonism can provide additive weight loss when combined with a glucagon-like peptide 1 (GLP-1) (GLP-1R) agonist. In this review, we examine motivated initiation of these seemingly contradictory drug discovery programs. We focus on physiologic role GIP in humans, human genetics evidence, rodent genetic models, preclinical non-human primate pharmacology studies. Furthermore, highlight where early findings translated into relevant efficacy development tirzepatide maridebart cafraglutide (MariTide).

Язык: Английский

Процитировано

0