What are incretins? They're hormones your gut releases when you eat, and their main job is to tell the pancreas to put out more insulin in a glucose-dependent manner, when blood sugar is high. Humans have two known incretins, GIP and GLP-1. Both are gone from the blood within minutes.
That answer sits under a lot of modern medicine. Semaglutide is built to act like GLP-1. Tirzepatide acts on the receptors for both hormones, which is why it's called a dual incretin drug. And a group of diabetes pills keeps your own incretins around longer.
What are incretins, officially?
The National Library of Medicine's medical vocabulary, MeSH, defines incretins as "peptides which stimulate insulin release from the pancreatic beta cells following oral nutrient ingestion, or postprandially." Beta cells are the insulin-making cells in the pancreas. Postprandially just means after a meal.
Drug labels add the key condition. The prescribing information for sitagliptin (Januvia), revised July 2023, says that "when blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release" (DailyMed).
That condition is what glucose-dependent means. An incretin works like a volume knob on a signal glucose has already started: high blood sugar, more insulin; normal blood sugar, little to amplify.
GIP and GLP-1, the two incretin hormones
The two come from different stretches of the gut. GIP, short for glucose-dependent insulinotropic polypeptide, is made by K cells in the upper gut. GLP-1, glucagon-like peptide-1, is made by L cells lower down (Nauck and Meier, 2018).
Both push insulin up when glucose is high. GLP-1 also lowers glucagon, the pancreatic hormone that tells the liver to release sugar, and slows the stomach. GIP's original name, gastric inhibitory polypeptide, came from its effects on stomach acid and movement, before its insulin role was known (Müller et al., 2019).
Tirzepatide is the medicine that uses both: its label says it activates "both the GIP and GLP-1 receptors, the targets for native GIP and GLP-1" (Mounjaro label, revised August 2026).
What is the incretin effect?
The word is older than the proof. Between 1929 and 1932, Edgard Zunz and Jean La Barre named a blood-sugar-lowering gut extract "incretin" (Müller et al., 2019). The proof came in 1964, when two groups reported the same surprise: glucose taken by mouth drew out far more insulin than glucose given into a vein (Elrick et al., 1964; McIntyre et al., 1964). In 1967, a study of lean, obese and diabetic volunteers found the insulin response to glucose by vein was "only 30-40%" of the response to oral glucose (Perley and Kipnis, 1967).
That gap is the incretin effect. Same sugar, different route, very different insulin.
It was also a clue about diabetes. In a 1986 study of 14 people with type 2 diabetes and 8 matched healthy volunteers, incretins accounted for about 73% of the insulin response to a glucose drink in the healthy group and only 36% in the group with diabetes (Nauck et al., 1986). Later work traced much of that loss to a pancreas that responds poorly to GIP but largely keeps its response to GLP-1 (Nauck and Meier, 2018), a big reason GLP-1 became the model for the first incretin medicines. The scientists behind GLP-1 itself are a separate story: who discovered GLP-1.
Why natural incretins last only minutes
Your body switches incretins off almost as fast as it makes them. An enzyme in the blood called DPP-4 (dipeptidyl peptidase-4) clips two amino acids off the front of GIP and GLP-1, and the clipped hormones no longer trigger insulin (Mentlein et al., 1993).
The result is a tiny half-life, the time it takes for half of something to clear. For native GLP-1 it is "around 1–2 min," thanks to DPP-4 and the kidneys (Müller et al., 2019). In one study, intact GIP's half-life was about 7 minutes in healthy volunteers (Deacon et al., 2000). Fine for a body that sends a fresh pulse with every meal; useless for a medicine.
Drug makers solved it two ways. One was to redesign the hormone. The Ozempic label, revised May 2026, calls semaglutide "a GLP-1 analogue with 94% sequence homology to human GLP-1" that is "stabilized against degradation by the DPP-4 enzyme." It also binds albumin, a common blood protein, which stretches its half-life to about one week (DailyMed). How semaglutide works walks through that design. The other fix was to leave the hormone alone and slow the enzyme.
Incretin drugs: incretin mimetics and DPP-4 inhibitors
Those two fixes became the two families of incretin drugs. A 2006 review in The Lancet named them "incretin mimetics," degradation-resistant drugs that switch on the GLP-1 receptor, and "incretin enhancers," DPP-4 inhibitors that protect your own hormones (Drucker and Nauck).
| Family | What it does | Examples | Usual form |
|---|---|---|---|
| GLP-1 receptor agonists ("incretin mimetics") | A long-lasting drug switches on the GLP-1 receptor | Exenatide, liraglutide, dulaglutide, semaglutide | Injection; oral semaglutide is a daily tablet |
| Dual GIP and GLP-1 receptor agonist | One molecule switches on both incretin receptors | Tirzepatide | Weekly injection |
| DPP-4 inhibitors ("incretin enhancers") | Slows the enzyme so your own GIP and GLP-1 last longer | Sitagliptin, saxagliptin, linagliptin, alogliptin | Daily pill |
The families don't behave alike. That review reported that GLP-1 drugs of the time lowered HbA1c, a three-month blood sugar average, by 1 to 2 percentage points with 2 to 5 kg of weight loss; DPP-4 inhibitors lowered it by 0.5 to 1.0 points "with few adverse events and no weight gain." So not every incretin drug is a weight-loss drug.
As of September 23, 2026, the day this article was written, the mimetic family even includes a non-peptide: Foundayo (orforglipron), a daily pill first approved in April 2026 that its label calls "a GLP-1 receptor agonist" (prescribing information).
Why tirzepatide is called a dual incretin drug
Tirzepatide's label says it "is based on the GIP sequence" and calls it "a GIP receptor and GLP-1 receptor agonist," with a half-life of about five days. One molecule, two incretin receptors, one weekly shot. That's all "dual" means.
Before tirzepatide, every incretin mimetic on the market targeted GLP-1 alone. How much each receptor contributes is still being worked out; how tirzepatide works covers what is known.
How incretins show up in a prescription
On a prescription, the word tells you what a medicine copies. "Incretin-based therapy" is now the umbrella term. As of September 23, 2026, the day this article was written, a recent example is a consensus statement from European obesity, dietitian and patient groups, published online July 8 and in the September issue of The Lancet Diabetes & Endocrinology (Dobbie et al., 2026). It focuses on what surrounds the drug: protein and resistance exercise to help protect muscle, diet quality, psychological screening, and shared decisions about starting, adjusting, pausing or stopping.
Through Promise, tirzepatide and semaglutide are dispensed as compounded medications, which is different from an FDA-approved product: the formulations offered here are not FDA-approved. A licensed provider may still prescribe a compounded formulation; that decision is between the patient and the doctor.
Mistakes people make with the word
Treating "incretin" and "GLP-1" as synonyms. GLP-1 is one of two. The shorthand leaves out GIP, and tirzepatide's second target.
Hearing "glucose-dependent" as "can't cause low blood sugar." Paired with insulin or a sulfonylurea, a pill that forces insulin release, the Mounjaro label warns of "an increased risk of hypoglycemia, including severe hypoglycemia."
Calling every hormone in a new combination an incretin. Some drugs in development add glucagon, a pancreatic hormone that raises blood sugar. A triple agonist is not a triple incretin.
Related terms
GLP-1 receptor agonist: a drug that switches on the GLP-1 receptor; is semaglutide a GLP-1? explains the class name. Bioavailability: how much of a dose reaches the blood (what is bioavailability). Boxed warning: the thyroid C-cell warning on long-acting GLP-1 drugs (what is a boxed warning).
At Promise, a licensed provider reviews every request and decides whether an incretin medicine fits your history. Not everyone qualifies.
