Before GLP-1 became famous, there was GIP. It was the first incretin hormone ever identified, it was discovered in a physiology laboratory at the University of British Columbia, and after decades in GLP-1’s shadow it now sits at the centre of some of the most effective metabolic drugs in development.
This guide covers how GIP was found and renamed, what it does, how it differs from GLP-1, the puzzle of why drug developers are both activating and blocking its receptor, and which research compounds act on it.
The short answer
- GIP (glucose-dependent insulinotropic polypeptide) is a 42-amino-acid hormone released by K cells in the upper small intestine after a meal.
- It was discovered between 1969 and 1971 by John C. Brown’s group at UBC, purified with Viktor Mutt at Stockholm’s Karolinska Institute, and first named gastric inhibitory polypeptide for its effect on stomach acid.
- In 1973, John Dupré of McGill University and Brown showed that GIP boosts insulin release when blood sugar is high, and the hormone was renamed. The new name was settled in discussions at the UBC Faculty Club.
- GIP and GLP-1 together produce the incretin effect. In type 2 diabetes the insulin response to GIP is markedly blunted, one reason GLP-1 drugs came first.
- Drug developers now both activate the GIP receptor (tirzepatide, retatrutide) and block it (Amgen’s MariTide), a paradox still being worked out.
A discovery made in Vancouver
In 1968, John C. Brown, Raymond Pederson and Jill Dryburgh in UBC’s Department of Physiology began chasing an old idea: that the intestine releases a hormone, then called an enterogastrone, that slows stomach-acid secretion after food arrives. They found inhibitory activity in intestinal extracts, and in 1969–70 Brown spent a year as a Medical Research Council of Canada visiting scientist in Viktor Mutt’s laboratory at the Karolinska Institute in Stockholm, where the factor was purified. The amino-acid sequence was completed in Vancouver late in 1970. The new 42-amino-acid hormone was named gastric inhibitory polypeptide.
In Stockholm in June 1970, Brown met another Canadian, John Dupré of McGill University, who suspected the new hormone might be the long-sought “incretin,” a gut signal that amplifies insulin release. Dupré was right. In a 1973 study in healthy volunteers, Dupré and Brown showed that infusing purified GIP together with glucose increased insulin secretion and improved glucose tolerance. Because this insulin effect turned out to be its most important role, the hormone was given a new name that kept the acronym: glucose-dependent insulinotropic polypeptide. Later work showed it is only a weak inhibitor of stomach acid at natural concentrations. Our history of Canadian peptide discovery puts GIP alongside insulin and calcitonin.
What GIP does
- It is released by K cells in the duodenum and upper jejunum, in proportion to the meal, especially in response to glucose and fat.
- It amplifies insulin release only when glucose is elevated. That glucose dependence is built into how beta cells respond.
- It can raise glucagon when glucose is low, according to human studies, an effect that differs from GLP-1.
- It acts on fat tissue, where it promotes fat storage in animal studies, and on bone and brain.
- It is short-lived. The enzyme DPP-4 removes its first two amino acids within minutes, leaving GIP(3–42), which no longer stimulates insulin.
GIP vs GLP-1
| GIP | GLP-1 | |
|---|---|---|
| Made by | K cells, upper small intestine | L cells, lower small intestine and colon |
| Length | 42 amino acids | 30–31 amino acids (active forms) |
| Discovered | 1969–71, at UBC | Sequence predicted from the proglucagon gene in 1983; insulin role shown in 1987 |
| Insulin release | Increases it, glucose-dependently | Increases it, glucose-dependently |
| Glucagon | Can increase it when glucose is low | Suppresses it when glucose is high |
| Stomach emptying | Little effect | Slows it |
| In type 2 diabetes | Insulin response markedly blunted | Response largely preserved |
| Drug approaches | Receptor activation in tirzepatide and retatrutide; blockade in MariTide | Many approved agonists, from liraglutide to semaglutide |
Why GLP-1 came first
In 1993, a study led by Michael Nauck found that in people with type 2 diabetes, GLP-1 still boosted insulin release strongly while GIP had largely lost that ability. For drug developers the conclusion seemed obvious: target GLP-1. GIP spent the next two decades as the less interesting incretin, while the GLP-1 field, shaped in part by Daniel Drucker’s work in Toronto, produced liraglutide, semaglutide and their successors. Our GLP-1 research map covers that lineage.
Incretin-class research compounds, each with a batch-matched COA.
View retatrutideThe GIP paradox: activate or block?
Animal genetics pointed one way. In 2002, mice lacking the GIP receptor were found to resist obesity on a high-fat diet, suggesting that blocking GIP might help with weight. Clinical results then pointed the other way: tirzepatide, which activates both GIP and GLP-1 receptors, produced more weight loss than GLP-1 activation alone, including in a head-to-head trial against semaglutide published in 2025. Retatrutide adds glucagon-receptor activation on top.
Meanwhile Amgen’s MariTide takes the opposite route, pairing an antibody that blocks the GIP receptor with GLP-1-activating peptides, and it is in late-stage trials too. Proposed explanations for how both approaches could work include receptor desensitization, where prolonged activation ends up behaving like blockade; effects of GIP signalling in the brain on nausea and food intake; and changes in how fat tissue stores energy. No one yet knows which mechanism dominates in people.
GIP in research compounds
- Tirzepatide is built on the GIP sequence and activates both the GIP and GLP-1 receptors. It is an approved prescription medicine.
- Retatrutide activates GIP, GLP-1 and glucagon receptors and has completed four phase 3 trials. See what the TRIUMPH trials found.
- Laboratory tools for GIP biology include DPP-4-resistant agonists such as [D-Ala2]-GIP and truncated antagonists such as GIP(3–30)NH2, used to switch the receptor on or off in experiments.
The fatty-acid side chains that let tirzepatide and retatrutide last for days are explained in peptide half-life engineering.
Reasonably well established
- GIP is a major incretin that amplifies glucose-dependent insulin release.
- Its insulin effect is blunted in type 2 diabetes.
- Combining GIP- and GLP-1-receptor activation produced large weight loss in clinical trials.
Open questions
- Why both activating and blocking the GIP receptor appear to help with weight.
- What GIP signalling does in the human brain.
- The long-term effects of GIP-receptor drugs on fat tissue and bone.
RetatrutideGIP, GLP-1 and glucagon agonistView product and COA
SurvodutideGLP-1 and glucagon, no GIPView product and COA
CagrilintideAmylin analogue, a different pathwayView product and COA
Research use only. Research peptides from Pure Peptides Canada are laboratory reagents for in-vitro research. They are not Mounjaro, Zepbound or any approved drug, they are not for human or veterinary use, and nothing in this article is dosing or medical guidance.
Frequently asked questions
What is GIP?
GIP is a 42-amino-acid hormone released by K cells in the upper small intestine after a meal. It amplifies insulin release when blood glucose is high and, with GLP-1, accounts for the incretin effect.
What does GIP stand for?
Today it stands for glucose-dependent insulinotropic polypeptide. It was originally named gastric inhibitory polypeptide, for its effect on stomach acid, and renamed in the 1970s once its insulin-releasing role was shown.
Who discovered GIP?
John C. Brown and colleagues at the University of British Columbia, working with Viktor Mutt at the Karolinska Institute in Stockholm, between 1969 and 1971. John Dupré of McGill University and Brown showed its insulin-releasing effect in people in 1973.
How is GIP different from GLP-1?
Both amplify glucose-dependent insulin release, but GIP comes from K cells in the upper intestine and GLP-1 from L cells further down. GLP-1 suppresses glucagon and slows stomach emptying; GIP can raise glucagon when glucose is low and has little effect on stomach emptying.
Why do some drugs activate the GIP receptor while others block it?
Mice lacking the GIP receptor resist obesity, which suggested blocking it, yet drugs that activate it alongside GLP-1 produced large weight loss in trials. Proposed explanations include receptor desensitization and effects in the brain and fat tissue, but the answer isn’t settled.
Which research compounds act on the GIP receptor?
Retatrutide activates GIP, GLP-1 and glucagon receptors. Tirzepatide, an approved medicine, activates GIP and GLP-1 receptors. Laboratories also use tools such as the agonist [D-Ala2]-GIP and the antagonist GIP(3–30)NH2.
Incretin research, from Vancouver to today
Research-grade incretin-class compounds with independent, batch-matched COAs and tracked delivery from inside Canada.
References
- Pederson RA, McIntosh CHS. Discovery of gastric inhibitory polypeptide and its subsequent fate: personal reflections. J Diabetes Investig. 2016;7(Suppl 1). PMC
- Brown JC. Gastric Inhibitory Polypeptide. Monographs on Endocrinology. Berlin: Springer; 1982. Springer
- Dupré J, Ross SA, Watson D, Brown JC. Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab. 1973;37(5):826–828.
- Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993;91(1):301–307.
- Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002;8(7):738–742.
- Coskun T, Sloop KW, Loghin C, et al. 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. Mol Metab. 2018;18:3–14.
- Health Canada. Summary Basis of Decision for Mounjaro (tirzepatide injection); Notice of Compliance November 24, 2022. Drug and Health Product Portal
- Eli Lilly Canada. Zepbound KwikPen (tirzepatide injection) now approved and available in Canada. July 9, 2025. Lilly Canada
For laboratory research use only. Not for human or veterinary use. This article summarizes published research for educational purposes and is not medical advice. Nothing here is intended to diagnose, treat, cure or prevent any disease.