GIP
The forgotten incretin, written off for decades and now one half of the best-selling obesity drugs
GIP is a 42-amino-acid gut hormone released after a meal that makes the pancreas release insulin when glucose is high. For years it was considered the weaker incretin and useless in type 2 diabetes. Then tirzepatide and retatrutide were built to hit its receptor alongside GLP-1.
What is it?
GIP is released by cells of the upper small intestine when food arrives and tells the pancreas to release insulin, but only when blood glucose is already raised, which is what makes incretins attractive: they do not push glucose down when it is normal.
Its reputation was poor for a long time. A 1984 infusion study in volunteers asked whether GIP works at physiological levels at all, and found no enhancement of insulin release at lower glucose loads, with a doubling only at the highest. That ambiguity, plus a weak response in type 2 diabetes, is why GIP was set aside while GLP-1 drugs were developed.
The reversal came from combination. Tirzepatide activates both receptors at once, and its phase 3 programme showed control and weight loss beyond what a GLP-1 drug alone produced; a mechanistic analysis found improvements in beta-cell function markers as well. GIP itself is still not a medicine.
The hormone has other roles that are now being probed: a receptor blocker was used to test whether GIP explains the paradoxical growth hormone rise seen in some people with acromegaly.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
These are the studies in people, read from their PubMed abstracts: two tirzepatide trials, one receptor-blocking study and the old infusion study that shaped the field.
The dual agonist in type 2 diabetes
SURPASS-1, a 40-week double-blind randomised placebo-controlled phase 3 trial across 52 centres in four countries, tested tirzepatide, which activates the GIP and GLP-1 receptors together, as sole treatment in people with type 2 diabetes not controlled by diet and exercise.
What the GIP arm appears to add
A post-hoc analysis of 316 people with type 2 diabetes compared tirzepatide, the GLP-1 drug dulaglutide and placebo. Markers of beta-cell function improved with tirzepatide at 5, 10 and 15 mg and with dulaglutide, and the proinsulin ratios fell further with tirzepatide at 10 and 15 mg than with placebo or dulaglutide.
The study that made GIP look weak
Volunteers were infused with 10, 20 or 40 g of intravenous glucose with or without GIP. No significant enhancement of insulin release was seen at 10 or 20 g; at 40 g the insulin response doubled, and tripling the GIP dose raised it further. The authors asked in their title whether this was physiology or pharmacology.
Blocking the receptor, in acromegaly
Twenty-five untreated patients with acromegaly each underwent a glucose tolerance test with placebo and with an infusion of the GIP receptor blocker GIP(3-30)NH2, to test whether GIP drives the paradoxical growth hormone rise about 30% of them show.
Side Effects & Contraindications
Reported Side Effects
GIP itself is given only in research infusions.
Contraindications & Cautions
Not a medicine.
Legal Status
The hormone is not a drug; the drugs built on its receptor are.
Frequently Asked Questions
?What does GIP do?
It is released by the upper small intestine after a meal and tells the pancreas to release insulin when blood glucose is already raised.
?Why was it ignored for so long?
Early human work suggested it does little at ordinary levels: an infusion study found no insulin enhancement at lower glucose loads, and the response is weak in type 2 diabetes.
?Why does it matter now?
Tirzepatide activates the GIP and GLP-1 receptors together and outperformed a GLP-1 drug alone, which revived interest in the receptor.
?Can you buy GIP?
GIP itself is not a medicine anywhere. What is approved is tirzepatide, a manufactured dual agonist, which is a different molecule.
References
- [pubmed] Rosenstock J, et al. "Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial." Lancet, 2021;398(10295):143-155. PMID: 34186022.
- [pubmed] Thomas MK, et al. "Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes." J Clin Endocrinol Metab, 2021;106(2):388-396. PMID: 33236115.
- [pubmed] Sarson DL, et al. "Glucose-dependent insulinotropic polypeptide augmentation of insulin. Physiology or pharmacology?." Diabetes, 1984;33(4):389-93. PMID: 6368294.
- [pubmed] Jensen MH, et al. "GIP Receptor Antagonism Eliminates Paradoxical Growth Hormone Secretion in Some Patients With Acromegaly." J Clin Endocrinol Metab, 2025;110(3):715-729. PMID: 39172542.
- [pubmed] Nauck MA, et al. "The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions." Lancet Diabetes Endocrinol, 2016;4(6):525-36. PMID: 26876794.
- [pubmed] Campbell JE, et al. "Pharmacology, physiology, and mechanisms of incretin hormone action." Cell Metab, 2013;17(6):819-837. PMID: 23684623.
Sources & Citations
Studies were read from their PubMed abstracts on October 1, 2026; the US status was checked in Drugs@FDA the same day.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.