When we talk about metabolic peptides, one name comes up everywhere: GLP-1. His cousin, GIP, remained in the shadows for three decades — before returning to the center of today's most studied molecules.
Two hormones for the same signal
After a meal, the intestine notifies the pancreas that nutrients are arriving. This message goes through two hormones, called incretins : GLP-1 (glucagon-like peptide-1), secreted by the lower part of the intestine, and GIP (glucose-dependent insulinotropic polypeptide), secreted by the upper part.
GIP is also the first of the two to have been identified, in the 1970s. Together, they explain why the same intake of glucose triggers much more insulin when it passes through the digestive tract than when it is administered directly into the blood. This is called the incretin effect.
What sets them apart
| GLP-1 | GIP | |
|---|---|---|
| Origin | Distal intestine (ileum, colon) | Proximal intestine (duodenum) |
| Amino acids | 30 or 31 | 42 |
| On insulin | Stimulates | Stimulates |
| On glucagon | Slows | Stimulates when blood sugar is low |
| On the stomach | Slows down draining | Weak effect |
| Adipose tissue | Indirect effect | Directly present receptors |
The most interesting line is the last one. GIP acts directly on fat cells, while GLP-1 mainly passes through the brain and the digestive system. Two different pathways to the same metabolism.
Thirty years of exclusion
In the 1990s, an observation ruled out GIP: in people with type 2 diabetes, its ability to trigger insulin collapses, while that of GLP-1 remains largely intact. A hormone that no longer works in affected patients is of no interest to anyone. Research therefore focused on GLP-1, from which the best-known molecules come.
Two observations relaunched the trail. First, this loss of response is not definitive: by normalizing blood sugar, sensitivity to GIP increases. Then, both blocking and prolonged stimulation of its receptor produce, in animal models, favorable metabolic effects — a paradox still discussed today.
The return by multiple agonists
The tirzepatide was the first molecule to activate both receptors, GLP-1 and GIP, in the same 39 amino acid sequence. THE R3TA goes further by adding the receptor of glucagon : three targets, three metabolic pathways.
This is what distinguishes successive generations, a subject detailed in our guide R3TA, tirzepatide, semaglutide. GIP is therefore no longer a historical curiosity: it is one of the three pillars of the most studied molecules in metabolism.
Where does research stand?
The exact role of GIP remains debated, particularly whether its receptor must be stimulated or blocked to obtain a metabolic benefit. Both approaches yielded results in the laboratory, which is rare and uncomfortable for researchers.
As with all molecules in this family, the products sold here are intended exclusively for laboratory research, without marketing authorization.
Fact sheet
- Last name
- GIP (glucose-dependent insulinotropic polypeptide)
- Structure
- 42 amino acids
- Origin
- K cells of the duodenum and jejunum
- Receptor or target
- GIP receptor (GIPR)
- Published half-life
- A few minutes, broken down by the enzyme DPP-4
- Molecules that activate it
- Tirzepatide, retatrutide
What the research says
Summary of published data, written by the PeptidLab team. It describes molecules studied in the laboratory or in clinical trials: nothing here is an indication for use.
1971DiscoveryCan J Biochem
Brown and Dryburgh publish the complete sequence of the peptide, then called "gastric inhibitory polypeptide".
1973Human studyJ Clin Endocrinol Metab
Dupré and colleagues show that GIP stimulates insulin secretion in humans when blood glucose is high.
1993Human studyJ Clin Invest
Nauck and colleagues observe that the insulinotropic effect of GIP is almost lost in type 2 diabetes, whereas that of GLP-1 is preserved. This is what led GIP to be set aside for years.
2018Phase 2The Lancet
The first dual GIP and GLP-1 agonist (the future tirzepatide) gives better results than dulaglutide: GIP becomes a research target again.
Sources
Links to PubMed or to the original document. Articles in English.
- Brown JC, Dryburgh JR. A gastric inhibitory polypeptide. II. The complete amino acid sequence. Can J Biochem, 1971. PubMed
- Dupré J et al. Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab, 1973. PubMed
- Nauck MA 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. PubMed
- Frias JP et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes. The Lancet, 2018. PubMed
Updated October 2026.
Frequently asked questions
What is an incretin?
A hormone released by the intestine after a meal, which alerts the pancreas of the arrival of nutrients. The two main ones are GLP-1 and GIP.
What is the difference between GLP-1 and GIP?
GLP-1 stimulates insulin, slows stomach emptying and contributes to satiety. GIP also stimulates insulin, but also acts on adipose tissue and glucagon, and its receptor is present in the brain.
Why has the GIP been neglected for a long time?
Because its effect on insulin collapses in people with type 2 diabetes. It was long considered unusable, until work showed that this response could be restored.
Which peptides target the GIP receptor?
Tirzepatide, a double GLP-1 and GIP agonist, and R3TA, a triple agonist which adds the glucagon receptor.
This guide has an informative and scientific purpose. PeptidLab products are intended exclusively for laboratory research and are not intended for human or animal consumption.