Incretins are gut-derived hormones released in response to nutrient intake. The two that matter for this class are glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, usually shortened to GLP-1 and GIP. Both are peptides, both act on class B G-protein-coupled receptors, and both are cleared from circulation within minutes of release.
Almost everything distinctive about the synthetic compounds in this class follows from that last fact.
The [degradation](/blog/peptide-degradation-pathways) problem the class is built around
Native GLP-1 has a circulating half-life of roughly two minutes. The enzyme dipeptidyl peptidase-4, DPP-4, cleaves it near the N-terminus, and renal clearance removes what survives. A molecule that disappears that fast is difficult to study in any sustained way.
Synthetic analogues in this class are therefore engineered against that clearance, using a small number of recurring strategies.
- Substitution at the DPP-4 cleavage site, commonly replacing the alanine at position 8 with a residue the enzyme does not recognise.
- Fatty-acid acylation, attaching a lipid chain so the molecule binds reversibly to circulating albumin and is released slowly from that reservoir.
- Backbone modification such as alpha-aminoisobutyric acid substitution, which resists proteolysis generally rather than at one site.
The combination of these changes is what separates a compound with a half-life measured in minutes from one measured in days.
Single, dual and triple agonists
The class is usually organised by how many receptors a molecule engages.
- Single agonists act at the GLP-1 receptor alone. Semaglutide and liraglutide are the structurally best characterised examples.
- Dual agonists engage both GIP and GLP-1 receptors. Tirzepatide is the reference compound, built on a GIP-based backbone rather than a GLP-1 one.
- Triple agonists add glucagon receptor activity. Retatrutide is the compound most often named here.
Adding a receptor is not simply additive. Relative potency at each receptor is a design parameter, and two triple agonists with the same nominal targets can have very different activity ratios between them. This is why the class is described by its activity profile rather than by a receptor count alone.
Why these are long sequences
Most compounds in this class run to 30 to 40 residues, which is long by the standards of a research peptide catalog. That length has direct consequences a buyer sees on documentation.
- Crude purity before purification is lower, because stepwise coupling losses compound across more cycles.
- The impurity profile is more complex, with more deletion sequences possible.
- Manufacturing cost is higher per milligram, which is most of why this class prices above a ten-residue peptide.
- Analytical separation is harder, since a single-residue deletion in a 37-residue chain is chemically very close to the parent.
A certificate on a compound of this length deserves more attention to the chromatogram than to the headline purity figure.
Cagrilintide and the amylin branch
Not everything grouped commercially with the incretins is one. Cagrilintide is an amylin analogue, acting at calcitonin and amylin receptors rather than at GLP-1 or GIP. It appears alongside the class because it is studied in combination with it, as in the fixed combination usually called cagrisema.
Reading a catalog, it is worth separating what shares a receptor family from what shares a shelf.
What the analysis should show
For this class specifically, three certificate lines carry more weight than usual.
- Mass spectrometry, because an acylated compound has a distinctive expected mass and a missing lipid chain is a real and detectable failure mode.
- Net peptide content, because these are typically isolated as salts and the gap between vial weight and peptide mass is material at this molecular weight.
- The chromatogram itself, for the reason above: at this chain length the purity number alone conceals more than it reveals.
All compounds described here are supplied for laboratory research only.
For where this sits among the other molecules a catalogue carries, not everything in a peptide catalog is a peptide covers how the classes differ.