The incretin compound classes, explained
The metabolic research catalogue has grown quickly, and the compound names give little away about how they relate to each other. This primer maps the classes so that a compound can be placed before its individual profile is read.
Why incretins became a research focus
Incretins are gut hormones released in response to food intake that amplify insulin secretion. The two principal ones are GLP-1 and GIP.
Native incretins are degraded within minutes by DPP-4, which made them useless as research tools until analogues resistant to that degradation were engineered. Every compound in this section descends from that engineering problem.
The classes
Mono-agonists engage a single receptor. Semaglutide and liraglutide are GLP-1 mono-agonists, separated mainly by half-life — liraglutide circulates for roughly a day, semaglutide for roughly a week.
Dual agonists engage two. Tirzepatide targets GIP and GLP-1. Survodutide targets GLP-1 and glucagon — a different pairing, and therefore a different profile.
Triple agonists engage three. Retatrutide is the studied example, adding glucagon to the GIP/GLP-1 pair.
Amylin analogues sit outside the incretin axis entirely. Cagrilintide is a long-acting amylin receptor agonist acting on separate satiety signalling. CagriSema combines it with semaglutide, which is why it is classed as a combination rather than an agonist of a given order.
| Class | Receptors | Examples |
|---|---|---|
| GLP-1 mono-agonist | GLP-1 | Semaglutide, Liraglutide |
| Dual agonist (incretin) | GIP + GLP-1 | Tirzepatide, VK2735 |
| Dual agonist (glucagon) | GLP-1 + glucagon | Survodutide |
| Triple agonist | GIP + GLP-1 + glucagon | Retatrutide |
| Amylin analogue | Amylin | Cagrilintide |
| Combination | GLP-1 + amylin | CagriSema |
| Non-peptide oral | GLP-1 | Orforglipron |
Peptides versus small molecules
Everything above is a peptide, which is why it is supplied as an injectable — peptides are digested if swallowed.
Two developments work around that. Oral semaglutide pairs the peptide with SNAC, an absorption enhancer that shields it long enough to cross the gastric mucosa. Orforglipron takes a different route: it is not a peptide at all, but a small molecule that binds the GLP-1 receptor, so it survives digestion without assistance.
These distinctions matter for handling. Peptide injectables need cold-chain discipline; oral formulations behave like conventional small-molecule material.
For research use only. Not for human consumption, diagnostic, therapeutic or veterinary use. This material is provided for laboratory reference and is not medical advice.