GIPR Function in the Central Nervous System: Implications and Novel Perspectives for GIP-Based Therapies in Treating Metabolic Disorders

Once-Weekly Semaglutide in Adults with Overweight or Obesity

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Genetic studies of body mass index yield new insights for obesity biology

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Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1

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Glucagon-like peptide 1 (GLP-1)

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Inhibition of gastric inhibitory polypeptide signaling prevents obesity

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The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss

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LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept

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Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial

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Energy balance and its components: implications for body weight regulation

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Semaglutide lowers body weight in rodents via distributed neural pathways.

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Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans

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Engaging neuroscience to advance translational research in brain barrier biology

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Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain.

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Hindbrain Neurons as an Essential Hub in the Neuroanatomically Distributed Control of Energy Balance

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How May GIP Enhance the Therapeutic Efficacy of GLP-1?

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Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon‐like peptide‐1 receptor agonists: A systematic analysis of published clinical trials

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Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain

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Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells

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Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake

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The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling

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Hypothalamic nutrient sensing in the control of energy homeostasis

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The importance of weight management in type 2 diabetes mellitus

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Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure

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The role of nausea in food intake and body weight suppression by peripheral GLP-1 receptor agonists, exendin-4 and liraglutide

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GIF biology and fat metabolism

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Area postrema cell types that mediate nausea-associated behaviors

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Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models

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Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism

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Reasons for Discontinuation of GLP1 Receptor Agonists: Data from a Real-World Cross-Sectional Survey of Physicians and Their Patients with Type 2 Diabetes

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Separate and combined glucometabolic effects of endogenous glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 in healthy individuals.

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A genetic map of the mouse dorsal vagal complex and its role in obesity

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GIP-Overexpressing Mice Demonstrate Reduced Diet-Induced Obesity and Steatosis, and Improved Glucose Homeostasis

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Parabrachial Calcitonin Gene-Related Peptide Neurons Mediate Conditioned Taste Aversion

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Effect of gastric inhibitory polypeptide on plasma levels of chylomicron triglycerides in dogs.

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Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism

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Regulation of human subcutaneous adipose tissue blood flow

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The Gluco- and Liporegulatory and Vasodilatory Effects of Glucose-Dependent Insulinotropic Polypeptide (GIP) Are Abolished by an Antagonist of the Human GIP Receptor

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AVP neurons in the paraventricular nucleus of the hypothalamus regulate feeding

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Differential Antidiabetic Efficacy of Incretin Agonists Versus DPP-4 Inhibition in High Fat–Fed Mice

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A novel <scp>GIP</scp> analogue, <scp>ZP</scp> 4165, enhances glucagon‐like peptide‐1‐induced body weight loss and improves glycaemic control in rodents

Nørregaard, P. K., Deryabina, M. A., Tofteng Shelton, P., Fog, J. U., Daugaard, J. R., Eriksson, P., Larsen, L. F., & Jessen, L. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13034 · Cited by 116 · see citing works

Central administration of GLP-1 and GIP decreases feeding in mice

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Gut-derived GIP activates central Rap1 to impair neural leptin sensitivity during overnutrition

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A survey of the mouse hindbrain in the fed and fasted states using single-nucleus RNA sequencing

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Long-Acting Glucose-Dependent Insulinotropic Polypeptide Ameliorates Obesity-Induced Adipose Tissue Inflammation

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Glucose-dependent insulinotropic polypeptide (GIP) receptor antagonists as anti-diabetic agents

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Leveraging the Gut to Treat Metabolic Disease

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Effect of Exogenous or Endogenous Gastric Inhibitory Polypeptide (GIP) on Plasma Triglyceride Responses in Rats

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Gastric inhibitory polypeptide (GIP) binding sites in rat brain

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Physiological roles of the GIP receptor in murine brown adipose tissue

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GIP receptor mRNA expression in different fat tissue depots in postmenopausal non-diabetic women

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Pharmacological antagonism of the incretin system protects against diet-induced obesity

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Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high fat fed mice

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The blunted effect of glucose-dependent insulinotropic polypeptide in subcutaneous abdominal adipose tissue in obese subjects is partly reversed by weight loss

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Arcuate nucleus and lateral hypothalamic CART neurons in the mouse brain exert opposing effects on energy expenditure

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Gastric Inhibitory Polypeptide and its Receptor are Expressed in the Central Nervous System and Support Neuronal Survival

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Beyond Glucagon-like Peptide-1: Is G-Protein Coupled Receptor Polypharmacology the Path Forward to Treating Metabolic Diseases?

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The postprandial response of gastric inhibitory polypeptide to various dietary fats in man.

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Absence of GIP secretion alleviates age-related obesity and insulin resistance

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Nutritional signals rapidly activate oligodendrocyte differentiation in the adult hypothalamic median eminencePreprint

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Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis

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Hypothalamic and brainstem glucose-dependent insulinotropic polypeptide receptor neurons employ distinct mechanisms to affect feeding

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GIPR Agonism Inhibits PYY-Induced Nausea-Like Behavior

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Loss of Function Glucose-Dependent Insulinotropic Polypeptide Receptor Variants Are Associated With Alterations in BMI, Bone Strength and Cardiovascular Outcomes

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Review Article: <scp>GLP</scp> ‐1 Receptor Agonists and Glucagon/ <scp>GIP</scp> / <scp>GLP</scp> ‐1 Receptor Dual or Triple Agonists—Mechanism of Action and Emerging Therapeutic Landscape in <scp>MASLD</scp>

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Spectrum of Phenotypes and Causes of Type 2 Diabetes in Children

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Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison

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Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes

Kaneko, S. (2022) · touchREVIEWS in Endocrinology · doi:10.17925/ee.2022.18.1.10 · Cited by 35 · see citing works

Fear circuit–based neurobehavioral signatures mirror resilience to chronic social stress in mouse

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Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists

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The antiemetic actions of GIP receptor agonism

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Roles of glucose‐dependent insulinotropic polypeptide in diet‐induced obesity

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The role of GIPR in food intake control

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GIPR Agonism Enhances TZD-Induced Insulin Sensitivity in Obese IR Mice

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GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective

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A Contemporary Rationale for Agonism of the GIP Receptor in the Treatment of Obesity

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The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs

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Insights into the Mechanism of Action of Tirzepatide: A Narrative Review

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Neurochemical Basis of Inter-Organ Crosstalk in Health and Obesity: Focus on the Hypothalamus and the Brainstem

Haspula, D., & Cui, Z. (2023) · Cells · doi:10.3390/cells12131801 · Cited by 11 · see citing works

A Mechanistic Rationale for Incretin-Based Therapeutics in the Management of Obesity

Samms, R. J., & Kusminski, C. M. (2024) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022724-105443 · Cited by 11 · see citing works

Spatiotemporal regulation of GIPR signaling impacts glucose homeostasis as revealed in studies of a common GIPR variant

Yammine, L., Picatoste, B., Abdullah, N., Leahey, R. A., Johnson, E. F., Gómez-Banoy, N., Rosselot, C., Wen, J., Hossain, T., Goncalves, M. D., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101831 · Cited by 11 · see citing works

Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits

Oteng, A., Liu, L., Cui, Y., Gavrilova, O., Lü, H., Chen, M., Weinstein, L. S., Campbell, J. E., Lewis, J. E., Gribble, F. M., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci182325 · Cited by 7 · see citing works

Insights into the neurobiology of weight loss after bariatric surgery and GLP-1R agonists

Cook, T. M., Fuller, K. N. Z., & Sandoval, D. A. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110269 · Cited by 7 · see citing works

Current and Future Pharmacological Interventions for Acquired Hypothalamic Obesity

Roth, C. L., Doelman-Oldenburger, N. J., & van Santen, H. M. (2026) · Drugs · doi:10.1007/s40265-025-02280-z · Cited by 7 · see citing works

Overlapping representations of food and social stimuli in VTA dopamine neuronsPreprint

Willmore, L., Minerva, A. R., Engelhard, B., Murugan, M., McMannon, B., Oak, N., Thiberge, S. Y., Peña, C. J., & Witten, I. B. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.17.541104 · Cited by 5 · see citing works

The role of the incretin GIP in inflammation

Rossi, G., Bucciarelli, L. G., Cimino, V., & Fiorina, P. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02719-w · Cited by 4 · see citing works

Systems genetics analysis of human body fat distribution genes identifies adipocyte processes

Reed, J. N., Jiansheng, H., Li, Y., Ma, L., Banka, D. S., Wabitsch, M., Wang, T., Ding, W. J., Björkegren, J., & Civelek, M. (2024) · Life Science Alliance · doi:10.26508/lsa.202402603 · Cited by 4 · see citing works

The Link between Three Single Nucleotide Variants of the GIPR Gene and Metabolic Health

Michałowska, J. M., Miller‐Kasprzak, E., Seraszek‐Jaros, A., Mostowska, A., & Bogdański, P. (2022) · Genes · doi:10.3390/genes13091534 · Cited by 4 · see citing works

Predicting 10‐year risk of type 2 diabetes in Chinese people with overweight or obesity treated with Tirzepatide: Post hoc analysis of SURMOUNT ‐ CN trial

Zhao, L., Tao, F., Cheng, Z., Lu, Y., Liu, M. R., Chen, H., Zhang, M., Yang, Y., Song, X. H., Sun, Y., et al. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16439 · Cited by 3 · see citing works

Targeting central pathway of Glucose‐Dependent Insulinotropic Polypeptide, Glucagon and Glucagon‐like Peptide‐1 for metabolic regulation in obesity and type 2 diabetes

Xu, Z., Wen, S., Dong, M., & Zhou, L. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16146 · Cited by 3 · see citing works

Islet Function and Insulin Secretion

Jones, P. M., & Persaud, S. J. (2024) · doi:10.1002/9781119697473.ch7 · Cited by 3 · see citing works

Revitalizing GIP: Therapeutic Potential in Metabolic and Neurodegenerative Disorders

Qiao, Y., Zhou, F., Mao, T., & Gao, L. (2026) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s559587 · Cited by 3 · see citing works

Gastric Inhibitory Polypeptide Receptor (GIPR) Overexpression Reduces the Tumorigenic Potential of Retinoblastoma Cells

Haase, A., Alefeld, E., Yalinci, F., Meenen, D. V., Busch, M. A., & Dünker, N. (2024) · Cancers · doi:10.3390/cancers16091656 · Cited by 2 · see citing works

Glucose-dependent insulinotropic peptide and beyond: co-agonist innovations in the treatment of metabolic diseases

Zhou, C., Gong, B., Liu, X., Hu, G., & Sun, L. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177681 · Cited by 2 · see citing works

Tirzepatide retention in iWAT with mesoporous polydopamine encapsulation enhances weight loss through leptin receptor signaling

Mi, L., Li, T., Xiang, X., Zhou, Y., Xiong, N., Chen, Y., Chen, J., Shang, S., Chen, S., Cheung, W. W., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.09.009 · Cited by 2 · see citing works

Glucose-dependent insulinotropic peptide (GIP) suppresses androgen biosynthesis in PCOS mouse models and cellular systems

Pan, M., Qian, Y., Jiang, L., Cao, C., & Li, L. (2025) · Gynecological Endocrinology · doi:10.1080/09513590.2025.2582506 · Cited by 1 · see citing works

The neuro-metabolic epidemic and the CB1R paradox

Vaccaro, F., Malta, G., Rizzo, M., Plescia, F., & Lavanco, G. (2026) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2026.102631 · Cited by 1 · see citing works

Neuropsychiatric association of tirzepatide and semaglutide in obesity with and without type 2 diabetes

Huang, Y., Liu, K.-W., Li, P., Chen, J.-C., Meyerowitz‐Katz, G., Su, P., & Huang, C. (2026) · Communications Medicine · doi:10.1038/s43856-026-01750-z · Cited by 1 · see citing works

Tirzepatide as a multi-organ integrator in metabolic diseases: a review of molecular mechanisms and clinical translation

Khan, I., Meenakshi, S., Abubakar, M., Kumar, N., Gaikwad, V. L., Rai, A., & Murti, K. (2026) · Endocrine · doi:10.1007/s12020-026-04686-5 · Cited by 1 · see citing works

One receptor, two opposite approaches: efficacy and tolerability of GIPR agonism and antagonism in obesity pharmacotherapy

Gao, S., & Borner, T. (2026) · Appetite · doi:10.1016/j.appet.2026.108723 · Cited by 1 · see citing works

Systems genetics analysis of human body fat distribution genes identifies Wnt signaling and mitochondrial activity in adipocytesPreprint

Reed, J. N., Jiansheng, H., Li, Y., Ma, L., Banka, D. S., Wabitsch, M., Wang, T., Ding, W. J., Björkegren, J., & Civelek, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.06.556534 · Cited by 1 · see citing works

Secretion and Impact of Gut Hormones in Obesity and Diabetes

Holst, J. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821618-7.00264-9

Identifying Biomarkers for Spinal Muscular Atrophy: A System Biology-Based Approach

Nourani, K. M., Demırel, H., & Şeytanoğlu, A. (2025) · International Workshop on Biomedical Applications, Technologies and Sensors (BATS) · doi:10.1109/bats67559.2025.11336168

High fat diet remodels the gene regulatory networks in the preoptic area

Lazaro, O., Beimfohr, C., App, B., Basu, R., Johnson, T. S., & Flak, J. N. (2026) · Scientific Reports · doi:10.1038/s41598-026-37692-8

Shortened Photoperiod Enhances Protein and Fat Energy Deposition in Growing Pigs

Cao, H., Zeng, Z., Shi, H., Wang, L., Li, Y., Hu, Q., Wang, L., & Zhang, S. (2026) · Animals · doi:10.3390/ani16040688

Emerging metabolic hormone therapeutics for metabolic dysfunction-associated steatohepatitis: incretin-based drugs, fibroblast growth factor analogs, and liver-targeting strategies

Han, S., Shin, J., Kim, J. C., & Na, D. H. (2026) · Journal of Pharmaceutical Investigation · doi:10.1007/s40005-026-00815-4

Semaglutide and Tirzepatide for the Treatment of MASH: What Works, What is Coming, and What is Missing

Chirapongsathorn, S., & Tacke, F. (2026) · Digestion · doi:10.1159/dig/acmag014

Structural basis for small-molecule agonism at GCGR and GIPR via a conserved intracellular allosteric site

Qian, H., Shan, H., Hu, W., Xu, H. E., & Zhao, L. (2026) · Acta Pharmacologica Sinica · doi:10.1038/s41401-026-01923-5

GLP-1, GIP, and Glucagon Receptor Agonism at the Obesity–Neurodegeneration Interface: A Narrative Review

Popa, E., Popa, A. E., Poroch, V., Schreiner, T. G., Slănină, A. M., Poroch, M., Hatneanu, A. M., Ungureanu, M. I., Petroaie, A. D., Bacușcă, A. I., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198738

The role of GIPR in food intake control

James-Okoro, P.-P., Lewis, J. E., Gribble, F. M., & Reimann, F. M. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1532076 · Cited by 18 · see citing works

GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice

Gutgesell, R. M., Khalil, A., Liśkiewicz, A., Maity‐Kumar, G., Novikoff, A., Grandl, G., Liśkiewicz, D., Coupland, C., Karaoglu, E., Akindehin, S., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01294-x · Cited by 56 · see citing works

Distinct brain regions mediate regulation of food intake in response to GIPR agonism or antagonism

Lewis, J. E., Montaner, M., Nuzzaci, D., James-Okoro, P.-P., Harada, N., Inagaki, N., Dodson, W. S., Knerr, P. J., Douros, J. D., Gribble, F. M., et al. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01575-z · Cited by 3 · see citing works

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

Liu, C. M., Killion, E. A., Hammoud, R., Lu, S.-C., Komorowski, R., Liu, T., Kanke, M., Thomas, V. A., Cook, K. D., Sivits, G. N., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01295-w · Cited by 37 · see citing works

Specific loss of GIPR signaling in GABAergic neurons enhances GLP-1R agonist-induced body weight loss

Wean, J., Kowalsky, A. H., Laker, R., Will, S., Drucker, D. J., Rhodes, C. J., & Seeley, R. J. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2024.102074 · Cited by 28 · see citing works