Overview
Glucose-dependent insulinotropic polypeptide (incretin hormone from intestinal K cells; its receptor is a target of dual and triple agonists.">GIP) is a 42-amino-acid hormone secreted by K-cells, which are concentrated in the duodenum and proximal jejunum. It was isolated in 1971 by John Brown and colleagues and initially named gastric inhibitory polypeptide because it reduced gastric acid secretion in dogs. When it became clear that its more significant physiological effect was glucose-dependent stimulation of insulin release, the name was revised while keeping the same abbreviation.
GIP was the first incretin hormone to be identified, and with GLP-1 it accounts for most of the incretin effect. Research in the 1990s showed that the insulinotropic response to GIP is reduced in type 2 diabetes, which for years dampened interest in it as a drug target. That changed with the development of dual GIP and GLP-1 receptor agonists, one of which, tirzepatide, is now an approved medicine. Meanwhile, GIPR antagonists are being explored as well, creating one of the most intriguing paradoxes in metabolic research. GIP is an endogenous peptide studied in incretin physiology, adipose biology and receptor pharmacology.
Mechanism studied
- K-cells
- GIP
- GIP receptor
- Insulin secretion
incretin hormone from intestinal K cells; its receptor is a target of dual and triple agonists.">GIP activates the GIP receptor (GIPR), a class B G protein-coupled receptor coupled to Gs and cAMP signalling. In beta cells this potentiates glucose-dependent insulin secretion. Unlike GLP-1, GIP can stimulate glucagon secretion from alpha cells, particularly at lower glucose levels. GIPR is expressed in adipose tissue, where GIP has been linked to increased blood flow, lipoprotein lipase activity and triglyceride uptake, and in bone and the central nervous system, including regions involved in nausea and food intake. DPP-4 cleaves GIP to inactive GIP(3-42). Prolonged agonist exposure causes GIPR desensitisation, which may help explain why agonists and antagonists can produce overlapping effects.
Research highlights
- 01Isolated in 1971 as gastric inhibitory polypeptide; renamed once its insulinotropic role was recognised.
- 02The reduced insulinotropic response to GIP in type 2 diabetes was a key finding of 1990s incretin research.
- 03GIPR knockout mice resist diet-induced obesity, supporting the hypothesis that GIP promotes fat storage.
- 04Dual GIP/GLP-1 receptor agonists reached approval, reviving interest in GIP receptor pharmacology.
- 05Open questions include how central GIPR signalling influences nausea and why both agonism and antagonism are being pursued.
Latest published research
6,521 papers on PubMed →Peptide LKLKLL is a more effective component of Akkermansia muciniphila which regulate glucolipid metabolism through GLP-1/GIP dual modulation
Li Y et al. · Gut microbes · 2026 Dec 31 · PMID 42473065
Determinants of variable response to GLP-1 receptor agonists: A mechanism-informed framework for precision treatment of obesity
Ghosal S et al. · Obesity pillars · 2026 Dec · PMID 42898214
Economic evaluation of tirzepatide, semaglutide, and liraglutide in the treatment of obese and overweight patients without diabetes: a short-term cost-effectiveness analysis in Iran
Reiszadeh N et al. · Journal of diabetes and metabolic disorders · 2026 Dec · PMID 42894545
Weight-Loss Outcomes After Sleeve Gastrectomy Versus Tirzepatide in a Minority Cohort With Severe Obesity: Results From a Propensity Score Matched Cohort
Manueli Laos EG et al. · Clinical obesity · 2026 Dec · PMID 42850698
Fat and lean mass changes during incretin-based therapy with structured exercise and nutritional support: A retrospective real-world pilot study
Kucuk Yetgin M et al. · Obesity pillars · 2026 Dec · PMID 42820241
Co-treating opioid and alcohol use disorders in the United States, 1960-2026: A historical policy review in the glucagon-like peptide-1 (GLP-1) era
Qeadan F et al. · Drug and alcohol dependence reports · 2026 Dec · PMID 42750843
Adaptive maintenance after incretin-induced weight loss: Moving beyond the continue-or-stop paradigm
van Bruggen FH et al. · Obesity pillars · 2026 Dec · PMID 42733607
Association of tirzepatide with reverse cardiac remodeling and improved diastolic function in obesity-related HFpEF: A prospective real-world cohort study
Karanxha J et al. · International journal of cardiology · 2026 Dec 1 · PMID 42710812
Live feed from PubMed (NCBI) for “GIP (Glucose-dependent Insulinotropic Polypeptide)”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.
Registered studies
270 on ClinicalTrials.gov →- Active not recruitingPhase 4
Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA) and Diet in Inflammatory Bowel Disease (IBD) Patients
NCT06774079 · University of Miami · 2025-03-05
- RecruitingPhase 4
Mechanisms of Weight Loss: Tirzepatide vs Semaglutide
NCT07900074 · McMaster University · 2026-10-31
- Recruiting
Prolongation of GLP-1 Adherence When Using Continuous Glucose Monitoring
NCT06668935 · Abbott Diabetes Care · 2024-10-24
- Recruiting
Insulin-Mediated Glucose Uptake and Organ Perfusion Assessed by Total-Body PET During GIP and GLP-1 Infusion
NCT07398300 · Copenhagen University Hospital, Rigshospitalet · 2026-03-12
- RecruitingPhase 2
Study of Olatorepatide in Adult Participants Living With Overweight or Obesity Without Diabetes
NCT07685808 · Regeneron Pharmaceuticals · 2026-07-28
- Not yet recruitingPhase 3
Efficacy And Safety of Olatorepatide in Adults With Overweight or Obesity Without Diabetes
NCT07896265 · Regeneron Pharmaceuticals · 2026-11-18
- Active not recruitingEarly Phase 1
A Study of a Weight Loss Intervention in People With Endometrial Cancer
NCT06751589 · Memorial Sloan Kettering Cancer Center · 2024-12-19
- RecruitingPhase 4
Resistance Training to Prevent Muscle Loss During Treatment With Tirzepatide
NCT07777575 · Technical University of Munich · 2026-10-07
From the public ClinicalTrials.gov registry for “GIP (Glucose-dependent Insulinotropic Polypeptide)”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.
Key references
- [1]Nauck & Meier, 2018 — Diabetes Obes Metab
- [2]PubMed — reviews on GIP and incretins
FAQ
It was first called gastric inhibitory polypeptide because early experiments showed it inhibited gastric acid secretion. Later work showed its principal role was stimulating insulin secretion in a glucose-dependent manner, so the name was changed to glucose-dependent insulinotropic polypeptide while retaining the abbreviation GIP.
Both are incretins, but they come from different cells, act on separate receptors and have distinct profiles. GIP is released more proximally in the gut, can stimulate glucagon at low glucose, does not slow gastric emptying appreciably and has prominent receptor expression in adipose tissue.
Researchers describe a paradox because both GIPR agonists and GIPR antagonists, when combined with GLP-1 receptor agonism, have been associated with reduced body weight in research. Proposed explanations include receptor desensitisation by sustained agonists and distinct central versus peripheral GIPR effects.
FOR RESEARCH USE ONLY.Not for human or veterinary use. Not intended to diagnose, treat, cure, or prevent any disease.