GLP-1 Receptor Agonists

What Defines a GLP-1 Receptor Agonist?

A compound belongs to this class when it activates the GLP-1 receptor. All three compounds here are long synthetic peptides, 31 to 39 amino acids, built on incretin hormone sequences [R1][R4][R5]. They share two design features:

• DPP-4 resistance. The amino acid at position 2 of the chain (position 8 in GLP-1 numbering) is swapped for aminoisobutyric acid (Aib) in semaglutide and tirzepatide; the semaglutide label states that this change protects the peptide from DPP-4 cleavage [R6][R7]. Retatrutide also carries Aib at position 2 [R5].
• Albumin binding. A lysine side chain carries a fatty diacid (C18 in semaglutide, C20 in tirzepatide) on a linker. The diacid binds plasma albumin and extends the half-life [R6][R7].

Single, Dual and Triple Agonists

The compounds differ in how many receptors they target. Semaglutide is a selective GLP-1R agonist [R1]. Tirzepatide acts on the GIP and GLP-1 receptors [R4]. Retatrutide acts on the GIP, GLP-1 and glucagon receptors [R5]. For receptor potency, half-life and published trial results side by side, see Retatrutide vs Tirzepatide vs Semaglutide.

Compounds in This Category

Sources: KEGG DRUG D10025, D11360, D12430 for formula, MW, sequence, targets and CAS [R1][R4][R5]; modifications from FDA labels and the discovery paper [R6][R7][R8].

Regulatory Status

Semaglutide and tirzepatide are active ingredients of FDA-approved prescription medicines [R9][R10]. The research materials sold here are not those medicines and are not approved drug products. Retatrutide is investigational and is not approved anywhere; FDA has stated it is not a component of any approved drug [R11]. FDA has also warned that products labeled "for research purposes" can still be treated as unapproved drugs when they are marketed for human use [R12]. Everything in this category is sold for laboratory research only. See RUO peptides explained.

GLP-1 Receptor Agonists FAQ

What is a GLP-1 receptor agonist?

It is a molecule that binds and activates the GLP-1 receptor, the receptor for the gut hormone glucagon-like peptide-1 [R1]. The compounds in this category are synthetic peptide analogues of incretin hormones.

What is the difference between a dual and a triple agonist?

A dual agonist such as tirzepatide activates two receptors, GIPR and GLP-1R. A triple agonist such as retatrutide also activates the glucagon receptor (GCGR) [R4][R5].

Why do these peptides last longer than native GLP-1?

In human plasma, native GLP-1 is cut by DPP-4 with a half-life of about 20 minutes in vitro [R2]. The analogues resist DPP-4 and bind albumin through their fatty diacid side chains [R6].

Are these research peptides the same as the prescription medicines?

No. Approved semaglutide and tirzepatide medicines are prescription drugs made and tested under FDA approval. Research-labeled material is not an approved product and is not for human use [R12].

How is each batch tested?

Each batch ships with a certificate of analysis showing HPLC purity and mass-spectrometry identity. Our guide How to read a peptide COA explains each line.

References

1. KEGG DRUG. Semaglutide (D10025). https://www.kegg.jp/entry/D10025
2. Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab. 1995;80(3):952-957. doi:10.1210/jcem.80.3.7883856. PMID 7883856
3. Lau J, Bloch P, Schäffer L, et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J Med Chem. 2015;58(18):7370-7380. doi:10.1021/acs.jmedchem.5b00726. PMID 26308095
4. KEGG DRUG. Tirzepatide (D11360). https://www.kegg.jp/entry/D11360
5. KEGG DRUG. Retatrutide (D12430). https://www.kegg.jp/entry/D12430
6. U.S. FDA. FDA prescribing information: semaglutide injection (NDA 209637), 2017. accessdata.fda.gov
7. U.S. FDA. FDA prescribing information: tirzepatide injection (NDA 215866), 2022. accessdata.fda.gov
8. Coskun T, Urva S, Roell WC, 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;34(9):1234-1247.e9. doi:10.1016/j.cmet.2022.07.013. PMID 35985340
9. U.S. FDA. Drugs@FDA: NDA 209637 (semaglutide), marketing status Prescription. accessdata.fda.gov
10. U.S. FDA. Drugs@FDA: NDA 215866 (tirzepatide), marketing status Prescription. accessdata.fda.gov
11. U.S. FDA, Office of Compounding Quality and Compliance. Letter to the Federation of State Medical Boards on retatrutide. March 31, 2025. azdo.gov (PDF)
12. U.S. FDA. FDA's concerns with unapproved GLP-1 drugs used for weight loss. fda.gov

For laboratory research use only. Not for human or veterinary use.