The compounds discussed here are supplied by RS Bio Labs strictly as laboratory research materials for qualified scientific personnel. They are not approved, intended or authorised for human consumption, self-administration, diagnostic, therapeutic or veterinary use. All findings referenced are from published preclinical or clinical-trial literature and do not constitute medical advice or establish safety in any unapproved setting.
What are incretins?
"Incretins" are gut-derived hormones released in response to nutrient intake that help the body coordinate blood glucose, insulin secretion and appetite. The two classical incretins are GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). A third hormone, glucagon, is not an incretin in the strict sense — it is a counter-regulatory hormone that raises glucose and mobilises stored energy — but it shares an ancestral peptide family with GLP-1 and GIP, and its receptor (GCGR) is engineered into the newest research molecules for a very specific reason.
Together these three receptor systems sit at different nodes of the body's energy-balance network: some reduce how much energy comes in, another increases how much energy goes out. Understanding what each one does individually is the key to understanding why combining them produces effects no single pathway can.
GLP-1 receptor (GLP-1R)
GLP-1 is the most extensively characterised of the three. Activation of the GLP-1 receptor produces glucose-dependent insulin secretion — insulin release scaled to blood glucose, which limits the risk of driving glucose too low. It also acts centrally on the hypothalamus and brainstem to promote satiety, and it slows gastric emptying so nutrients arrive more gradually. The net research signature is reduced energy intake. Semaglutide is the archetypal pure GLP-1 receptor agonist and defines the "appetite-suppressing" arm of the class.
GIP receptor (GIPR)
GIP is the other classical incretin and, like GLP-1, is insulinotropic — it augments glucose-dependent insulin secretion. Its distinct value in research comes from its effects on adipose tissue and lipid handling, and from evidence that co-activating GIPR alongside GLP-1R produces an additive metabolic effect greater than GLP-1 activation alone. On its own GIP is a comparatively modest lever, but as a partner to GLP-1 it is what lifted dual agonists a clear step beyond single-pathway compounds.
Glucagon receptor (GCGR)
Glucagon is the pathway that changes the equation. Where GLP-1 and GIP act largely on the "energy-in" side, glucagon-receptor activation is associated in research models with increased resting energy expenditure and with hepatic glycogenolysis and lipolysis — mobilising and burning stored energy. In isolation, raising glucagon would tend to increase blood glucose, which is why it is never used alone; but combined with the glucose-lowering GLP-1/GIP arms, it adds an "energy-out" component the appetite-suppressing pathways cannot supply. This is the mechanistic reason glucagon co-agonism is of such interest.
Mono-, dual- and triple-agonism
The progression of research in this class maps almost directly onto how many of these receptors a single molecule engages:
- Monoagonists — a single molecule targeting one receptor. Semaglutide (GLP-1) is the reference point: reduce intake via a single well-characterised pathway.
- Dual agonists — one molecule engineered to hit two receptors. Tirzepatide (GIP + GLP-1) stacks two "energy-in" incretin arms, while Mazdutide and Survodutide (GLP-1 + glucagon) pair an "energy-in" arm with an "energy-out" arm.
- Triple agonists — one molecule engaging all three. Retatrutide (GIP + GLP-1 + glucagon) is the leading example, combining both incretin arms with the glucagon energy-expenditure arm in a single peptide.
The appeal of engineering multiple pathways into one molecule — rather than combining several drugs — is that a single, long-acting peptide can deliver a coordinated, balanced signal across the whole energy-balance network at a fixed receptor ratio. Tuning that ratio is precisely what compound designers optimise, and it is why the triple-agonist mechanism sits at the current frontier.
| Compound | Receptor targets | Class |
|---|---|---|
| Semaglutide | GLP-1 | Mono |
| Tirzepatide | GIP + GLP-1 | Dual |
| Mazdutide | GLP-1 + Glucagon | Dual |
| Survodutide | GLP-1 + Glucagon | Dual |
| Retatrutide | GIP + GLP-1 + Glucagon | Triple |
| Cagrilintide | Amylin | Companion class |
A note on amylin: Cagrilintide is an amylin analogue, not an incretin agonist. Amylin is a related but separate pathway — a pancreatic hormone that reinforces satiety and slows gastric emptying — and it is studied as a companion to incretin agonists rather than as one of the three receptor systems above. It is included in the table only to show where it sits relative to the incretin/glucagon family.
The whole class comes down to one idea: reduce energy intake and increase energy expenditure at the same time. GLP-1 and GIP handle the "reduce intake" side; glucagon adds the "increase expenditure" side. Retatrutide embodies this by being the one molecule that engages all three at once — which is why the triple-agonist mechanism is described as combining both halves of the energy-balance equation in a single peptide.
Where this leaves the research picture
Reading the pathways this way makes the compound landscape easy to navigate. A monoagonist like Semaglutide works one lever; dual agonists add a second — either a second incretin arm (Tirzepatide) or the glucagon expenditure arm (Mazdutide, Survodutide); and the triple agonist Retatrutide combines all three. For a deeper look at the leading triple agonist, see What Is Retatrutide?, and for a direct dual-vs-triple comparison see Retatrutide vs Tirzepatide.
None of the compounds referenced here are approved medicines. Everything documented above is drawn from published clinical-trial and preclinical literature and is provided as a scientific reference only. Products sold by RS Bio Labs are research reagents for in vitro laboratory work and are not for human use.