GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are both "incretin" hormones released by the gut after eating, and both prompt the pancreas to release insulin in a glucose-dependent way. GIP is actually the dominant incretin hormone in people without diabetes, but its insulin-boosting effect weakens significantly in type 2 diabetes, which is part of why GLP-1 became the bigger drug target on its own. GLP-1 also has more direct effects on appetite and gastric emptying. Tirzepatide (Mounjaro, Zepbound) is a dual agonist that activates both the GIP and GLP-1 receptors at once, and it outperformed a selective GLP-1 drug on blood sugar and weight in a major head-to-head diabetes trial. Newer investigational drugs, like retatrutide, go further and add a third target (glucagon receptor), but retatrutide is not FDA-approved and is not available by prescription.
Key takeaways
- GLP-1 and GIP are both incretin hormones released by the gut in response to food, and both stimulate insulin release.
- GIP is the dominant incretin in healthy people, but its insulin effect is blunted in type 2 diabetes, unlike GLP-1's.
- Tirzepatide is a dual GIP/GLP-1 receptor agonist, not a pure GLP-1 drug.
- Retatrutide is an investigational triple agonist (GIP + GLP-1 + glucagon); it is not approved, and "GLP-3" is informal shorthand, not a real hormone class.
What are GLP-1 and GIP?
GLP-1 and GIP belong to a small family of hormones called incretins. Both are released from cells lining the small intestine within minutes of eating, and both travel to the pancreas to boost insulin release, but only when blood sugar is actually elevated, which is why they're described as "glucose-dependent." That built-in safety brake is a key reason incretin-based drugs carry a comparatively lower risk of causing low blood sugar on their own, compared with insulin or some older diabetes drugs.
Despite the shared basics, the two hormones aren't identical, and the difference matters clinically:
- GLP-1 stimulates glucose-dependent insulin secretion, suppresses glucagon (a hormone that raises blood sugar), slows gastric emptying, and reduces appetite through effects on the brain's satiety pathways. These extra effects are why GLP-1 receptor agonists became the basis for both diabetes and weight-management drugs.
- GIP is, in healthy people, actually the larger contributor to the overall "incretin effect" (the extra insulin response to food eaten by mouth versus given intravenously). But in type 2 diabetes, the insulin-stimulating effect of GIP is substantially reduced, while GLP-1's effect holds up much better. That's a major reason early incretin-based diabetes drugs targeted GLP-1 alone rather than GIP.
Interestingly, more recent research suggests GIP still plays a useful role when combined with GLP-1 activity, even in diabetes, which is part of the rationale behind dual-agonist drugs like tirzepatide.
Where does tirzepatide fit in?
Tirzepatide, sold as Mounjaro (for type 2 diabetes) and Zepbound (for chronic weight management), is a dual GIP/GLP-1 receptor agonist. Rather than choosing one incretin pathway, it's engineered to activate both the GIP receptor and the GLP-1 receptor. Research describes it as an "imbalanced" agonist: its activity at the GIP receptor is similar in strength to the body's own GIP, while its activity at the GLP-1 receptor is somewhat weaker than the body's own GLP-1, but still therapeutically meaningful.
In a major head-to-head diabetes trial (SURPASS-2), tirzepatide produced greater reductions in blood sugar (A1c) and body weight than a selective GLP-1 receptor agonist. That result is a big part of why dual-agonist and multi-agonist drugs became such an active area of development, GIP appears to add benefit on top of GLP-1 rather than simply being redundant with it. For more on how tirzepatide-based drugs compare with single-target semaglutide in practice, see our semaglutide vs tirzepatide comparison.
Single, dual, and triple agonists: a quick map
It helps to think of these medications on a spectrum, from targeting one incretin-system receptor to targeting several at once.
| Category | Receptor targets | Example drugs | Status |
|---|---|---|---|
| Single GLP-1 agonist | GLP-1 receptor only | Semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), exenatide (Byetta, Bydureon) | FDA-approved |
| Dual GIP/GLP-1 agonist | GIP receptor + GLP-1 receptor | Tirzepatide (Mounjaro, Zepbound) | FDA-approved |
| Investigational triple agonist | GIP + GLP-1 + glucagon receptors | Retatrutide | Not FDA-approved; in late-stage clinical trials |
What about retatrutide, and is "GLP-3" real?
Retatrutide (developed by Eli Lilly) is an investigational medication designed to activate GIP and GLP-1 receptors, like tirzepatide, plus a third target: the glucagon receptor. Mid-stage trial data reported substantial average weight loss, which drew significant media attention, but it's important to be precise about status: retatrutide is not FDA-approved, it is not available by prescription for weight loss or any other use, and its safety and efficacy are still being evaluated in ongoing trials.
You may see "GLP-3" used online as shorthand for retatrutide or similar triple agonists. That's not an official or recognized hormone or drug class, GLP-1 and GIP (and glucagon) remain the actual receptor targets involved; "GLP-3" is just informal marketing-style language, not a scientific term. For a broader look at what's in development, see our roundup of GLP-1 medications.
Why understanding the hormone science actually helps you
None of this changes what a prescriber decides for an individual patient, but understanding the underlying hormones helps make sense of why the GLP-1 drug landscape keeps expanding rather than settling on one "best" molecule. Each additional receptor target represents a genuine attempt to improve on blood-sugar control, weight loss, or both, based on the distinct roles GLP-1, GIP, and glucagon play in metabolism. It also explains why marketing language like "next-generation" or "triple-action" usually maps to something real in the mechanism, even when the specific drug is still years from approval.
If you're trying to understand how these hormones translate into currently available treatment options, our what is GLP-1 basics guide is the best starting point, and our Zepbound and tirzepatide guide covers the one approved dual-agonist drug in detail.
Frequently asked questions
What is the difference between GLP-1 and GIP?
Both are incretin hormones released by the gut after eating, and both trigger insulin release in a glucose-dependent way. GIP is actually the dominant incretin in people without diabetes, but its insulin-boosting effect is blunted in type 2 diabetes, while GLP-1's effect holds up better and GLP-1 also slows gastric emptying and reduces appetite more directly.
Is tirzepatide a GLP-1 or GIP drug?
Tirzepatide (Mounjaro, Zepbound) is a dual agonist, it activates both the GIP receptor and the GLP-1 receptor. It isn't purely one or the other; it's designed to engage both incretin pathways.
What is a dual or triple agonist?
A dual agonist activates two hormone receptors at once, as tirzepatide does with GIP and GLP-1. A triple agonist adds a third target; retatrutide, an investigational drug, is designed to activate GIP, GLP-1, and glucagon receptors, but it is not FDA-approved.
How is retatrutide different?
Retatrutide is being developed as a triple agonist that adds glucagon receptor activity on top of GIP and GLP-1. It has shown large average weight loss in mid-stage trials, but as of this writing it remains investigational and is not approved or available by prescription.
Sources & further reading
- U.S. Food & Drug Administration, prescribing information for Mounjaro and Zepbound (tirzepatide) injection.
- Peer-reviewed mechanism reviews on dual GIP/GLP-1 receptor agonism (tirzepatide), published in clinical pharmacology and cardiometabolic research journals.
- Peer-reviewed data on the SURPASS-2 head-to-head trial of tirzepatide versus a selective GLP-1 receptor agonist in type 2 diabetes.
- Manufacturer and peer-reviewed trial disclosures on retatrutide's investigational status (Eli Lilly).