Is GLP-1 a Peptide? GLP-1, Analogues and Co-Agonists

Yes, GLP-1 is a peptide. Glucagon-like peptide-1 is a hormone about 30 amino acids long, produced mainly by L-cells in the gut from the proglucagon precursor. The drugs and research compounds that act on its receptor, from semaglutide to tirzepatide and retatrutide, are also mostly peptides, modified so that they last days instead of minutes.

For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.

Key points

Native GLP-1 is a peptide hormone; active forms are GLP-1(7-36) amide and GLP-1(7-37).
GLP-1(7-37): C₁₅₁H₂₂₈N₄₀O₄₇, about 3356 g/mol.
Native GLP-1 is inactivated within minutes by DPP-4.
Long-acting analogues add DPP-4 resistance and albumin binding.
Co-agonists (tirzepatide, retatrutide) are peptides that hit GLP-1R plus other receptors.

What GLP-1 is

A 2019 review describes GLP-1 as a multifaceted hormone. Its effects include glucose-dependent stimulation of insulin secretion, slowing of gastric emptying and reduction of food intake, and it is also active in heart, kidney and brain (Müller et al., 2019). It is processed from proglucagon, the same precursor that gives rise to glucagon in the pancreas, which is why the names are similar.

Form	Length	Notes
GLP-1(1-37)	37 aa	Largely inactive precursor form
GLP-1(7-37)	31 aa	Active; ~3356 g/mol
GLP-1(7-36) amide	30 aa, C-terminal amide	Major active circulating form
GLP-1(9-36) amide	28 aa	DPP-4 product; much weaker at the receptor

From hormone to long-acting peptide

Native GLP-1’s short life in circulation made it unsuitable as a medicine. Medicinal chemists solved this in stages:

Generation	Example	Key change	Receptors
Native hormone	GLP-1(7-36) amide	None	GLP-1R
Acylated analogue, daily	Liraglutide	Fatty acid for albumin binding	GLP-1R
Acylated analogue, weekly	Semaglutide	Aib8 (DPP-4 resistance), Arg34, optimised fatty acid and linker	GLP-1R
Dual co-agonist	Tirzepatide	GIP-based sequence, Aib2/Aib13, C20 diacid	GIPR + GLP-1R
Triple co-agonist	Retatrutide	Single peptide engaging three receptors	GIPR + GLP-1R + GCGR

Semaglutide’s design shows the logic clearly: increasing albumin affinity through the fatty acid and linker, while securing stability against metabolic degradation, produced a once-weekly analogue (Lau et al., 2015). Tirzepatide extended the approach to two receptors (Coskun et al., 2018), and retatrutide to three (Coskun et al., 2022).

Are all “GLP” compounds GLP-1 agonists?

No, and the naming causes confusion:

GLP-2 is a separate proglucagon-derived peptide with intestinal growth effects; it acts on a different receptor.
“GLP-3” is not a real hormone. It is an informal online nickname for retatrutide, referring to its three receptor targets; see what is retatrutide?
Amylin analogues such as cagrilintide are peptides often studied alongside GLP-1 agonists, but they act on amylin and calcitonin receptors (Kruse et al., 2021); see what is cagrilintide?

Peptide vs small-molecule GLP-1 agonists

Because “peptide” refers to chemical structure, not to function, the answer to “is it a peptide?” can differ within the same drug class. Most licensed GLP-1 receptor agonists are peptides, including oral semaglutide, which uses an absorption enhancer. Several orally active small-molecule GLP-1 receptor agonists have also been developed; they activate the same receptor but are not peptides. For laboratory work this matters: peptides need peptide handling (cold storage, gentle reconstitution, protection from aggregation), whereas small molecules generally do not.

Handling incretin peptides in the lab

Lipidated incretin peptides are amphiphilic and can self-associate; swirl gently and avoid freeze–thaw.
Store powders at −20 °C and solutions at 2–8 °C.
At nanomolar working concentrations, use low-binding plastics. See reconstituting tirzepatide for in vitro work.
Calculate concentrations with the peptide reconstitution calculator.

Research-grade incretin peptides in our catalogue include tirzepatide and retatrutide.

Open questions

How much of the effect of co-agonists depends on each receptor in different tissues? Receptor-specific knockout and antagonist studies are still clarifying this.
Will small-molecule GLP-1 receptor agonists reproduce the full signalling profile of peptide agonists, including biased signalling at the receptor? Comparative data are emerging.

Related research

Frequently asked questions

Is GLP-1 a peptide?

Yes. Glucagon-like peptide-1 is a peptide hormone of about 30 amino acids, produced mainly by intestinal L-cells from the proglucagon precursor. The active forms are GLP-1(7-36) amide and GLP-1(7-37).

Are GLP-1 receptor agonists peptides?

Most are. Semaglutide, liraglutide, dulaglutide and exenatide are peptides, as are dual and triple agonists such as tirzepatide and retatrutide. Some newer oral GLP-1 receptor agonists in development are small molecules rather than peptides.

Are all peptides GLP-1 agonists?

No. ‘Peptide’ simply means a short chain of amino acids. GLP-1 receptor agonists are one small group among thousands of peptides with unrelated functions.

Is tirzepatide a GLP-1?

Tirzepatide is a peptide that activates the GLP-1 receptor, but it is based on the GIP sequence and also activates the GIP receptor, so it is usually described as a dual GIP/GLP-1 receptor agonist.

Why does native GLP-1 not last long in the body?

It is cleaved within minutes by the enzyme dipeptidyl peptidase-4 (DPP-4) and cleared by the kidneys. Therapeutic analogues are modified to resist DPP-4 and to bind albumin.

References

Müller TD, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019. PMID: 31767182 https://pubmed.ncbi.nlm.nih.gov/31767182/
Lau J, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015. PMID: 26308095 https://pubmed.ncbi.nlm.nih.gov/26308095/
Coskun T, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018. PMID: 30473097 https://pubmed.ncbi.nlm.nih.gov/30473097/
Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022. PMID: 35985340 https://pubmed.ncbi.nlm.nih.gov/35985340/
Kruse T, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021. PMID: 34288673 https://pubmed.ncbi.nlm.nih.gov/34288673/
PubChem Compound Summary for CID 16133830, GLP-1(7-37). National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/16133830