GLP-1 research peptides: semaglutide, tirzepatide, retatrutide and cagrilintide compared

Semaglutide, tirzepatide and retatrutide are lipidated peptides that act at one, two and three of the related receptors for GLP-1, GIP and glucagon. Cagrilintide is often shelved with them but is not a GLP-1 at all: it is an amylin analogue that acts at amylin and calcitonin receptors. As of October 21, 2026, semaglutide and tirzepatide are active ingredients of FDA-approved medicines, while retatrutide and cagrilintide are investigational. The tables below set out each molecule's parent hormone, length, modifications, receptors and molecular weight, with sources.

What is a GLP-1 research peptide?

"GLP-1 peptide" is used loosely for any peptide that acts at the GLP-1 receptor, and more loosely still for anything sold beside them. Strictly, the class has two families of molecule and two families of receptor.

The incretin family descends from gut and pancreatic hormones. GLP-1 and glucagon are both cut from the same precursor, proglucagon (UniProt P01275, gene GCG): glucagon is 29 residues and is secreted by the A cells of the pancreatic islets, and GLP-1(7-37) is 31 residues and is secreted by enteroendocrine cells of the gut. GIP, glucose-dependent insulinotropic polypeptide, comes from a different gene and is 42 residues long (UniProt P09681).

The amylin family descends from amylin, also called islet amyloid polypeptide, a 37-residue hormone with a disulfide loop near its start (UniProt P10997). Cagrilintide belongs here.

On this site all four sit on the GLP-1 and metabolic shelf, each as a lyophilized research vial labelled research use only.

GLP-1 vs GIP vs glucagon receptor: what is the difference?

They are three separate receptors, each named for the native hormone that activates it, and all three belong to the same structural group, the class B1 G protein-coupled receptors. The published cryo-EM structures of retatrutide bound to each of them number their residues on the common class B1 scheme, which is a measure of how closely related they are. Amylin receptors are built differently: the authors of the 2025 cagrilintide structures describe them as "heterodimers of the class B1 G protein-coupled receptor, calcitonin (CT) receptor (CTR), and receptor activity-modifying proteins (RAMPs)," giving AMY1R, AMY2R and AMY3R with RAMP1, RAMP2 and RAMP3.

That is the whole answer to "mono, dual or triple agonist": the count of receptors in the first three rows that a single molecule activates. It describes receptor activity in cells, not anything about a person.

The four molecules compared

Semaglutide's label describes the design in its own words: albumin binding "facilitated by modification of position 26 lysine with a hydrophilic spacer and a C18 fatty di-acid," a modification at position 8 "to provide stabilization against degradation by the enzyme dipeptidyl-peptidase 4 (DPP-4)," and "a minor modification" at position 34 "to ensure the attachment of only one fatty di-acid." Semaglutide is numbered on GLP-1's own scheme, which starts at 7, so its position 8 is the second residue of the chain.

The molecular weights also matter for identity testing. A mass spectrum separates all four at once, and a vial that matches the wrong number is the wrong molecule.

Each research vial has its own page: semaglutide, a 31-residue GLP-1 analogue; tirzepatide, a 39-residue GIP-based dual agonist; retatrutide, a 39-residue GIP-based triple agonist; and cagrilintide, a 37-residue lipidated amylin analogue.

What is the difference between semaglutide, tirzepatide and retatrutide?

Three differences carry most of the weight.

Parent sequence. Semaglutide is built on GLP-1. Tirzepatide and retatrutide are both built on GIP: both open with GIP's tyrosine followed by Aib, and both run to 39 residues.

Receptor count. Semaglutide is a GLP-1 receptor agonist only. Tirzepatide's label calls it "a GIP receptor and GLP-1 receptor agonist." Retatrutide adds the glucagon receptor; in cell-assay data summarised by Li and colleagues in 2024 it is more potent than native GIP at the GIP receptor and less potent than the native hormones at the GLP-1 and glucagon receptors.

Lipid and its position. Semaglutide carries a C18 diacid; tirzepatide and retatrutide carry C20 diacids, on lysine 20 and lysine 17 respectively.

The residue-by-residue detail is in the tirzepatide research reference and the retatrutide research reference, and the three are laid out together, with certificates, in semaglutide vs tirzepatide vs retatrutide and the two-way tirzepatide vs semaglutide.

Is cagrilintide a GLP-1?

No. Cagrilintide is a synthetic analogue of amylin, not of GLP-1. FDA's substance registry records it as 37 residues, KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP in one-letter code, with the cysteines at 2 and 7 bridged, a C20 fatty diacid joined through γ-glutamate to the first residue, and a C-terminal prolinamide. The 2025 structural paper calls it "a long-acting amylin and calcitonin receptor agonist" and shows it bound to the three amylin receptors and the calcitonin receptor, none of which is the GLP-1 receptor.

The confusion has two sources. Novo Nordisk is developing it in a co-formulation with semaglutide named CagriSema, and it shares the engineering idea of a fatty diacid that binds albumin. The full lineage from amylin through pramlintide is in cagrilintide is an amylin analogue, not a GLP-1.

The retatrutide and cagrilintide blend on this site is two separate peptides in one vial. Each keeps its own sequence and mass, so a certificate for it should identify both.

Which of these are FDA approved, as of October 21, 2026?

An approved medicine is a specific formulation, made and labelled under its application. A research vial of the same peptide is a laboratory material with a certificate for its lot and no label for any use in a person, and it is not any of the products named above. Retatrutide's regulatory record is set out in is retatrutide FDA approved? and tirzepatide's in is tirzepatide FDA approved?.

None of the four is a controlled substance, and WADA's 2026 Prohibited List names none of them. This site does not publish use guidance for any of them.

Frequently asked questions

What peptides are in the GLP-1 class?

Of the molecules on this shelf, semaglutide acts at the GLP-1 receptor alone, tirzepatide at the GIP and GLP-1 receptors, and retatrutide at the GIP, GLP-1 and glucagon receptors. Cagrilintide is shelved with them but is an amylin analogue.

What does GIP stand for?

Glucose-dependent insulinotropic polypeptide, a 42-residue gut hormone. UniProt records it under its older name, gastric inhibitory polypeptide. Tirzepatide and retatrutide are built on its sequence.

Is retatrutide a GLP-1?

It is a GLP-1 receptor agonist, but not a GLP-1 analogue in the narrow sense. Its 39-residue chain is built on GIP, and it activates the GIP, GLP-1 and glucagon receptors.

Why do these peptides carry a fatty acid?

To bind albumin. Semaglutide's label names albumin binding as its main protraction mechanism, and tirzepatide's says its C20 diacid "enables albumin binding." Retatrutide and cagrilintide carry C20 diacids on the same design idea.

Which is the largest molecule of the four?

Tirzepatide, at an average molecular weight of 4813.53, followed by retatrutide (4731), cagrilintide (4409) and semaglutide (4113.58).

Sources

• OZEMPIC (semaglutide) prescribing information, sections 11 and 12.1, DailyMed, published June 10, 2026
• MOUNJARO (tirzepatide) prescribing information, revised 8/2026, DailyMed
• Drugs@FDA: NDA 209637, Ozempic, read October 21, 2026
• Drugs@FDA: NDA 218316, Wegovy tablets, read October 21, 2026
• Drugs@FDA: NDA 215866, Mounjaro, read October 21, 2026
• Semaglutide, UNII 53AXN4NNHX, FDA Global Substance Registration System
• Cagrilintide, UNII AO43BIF1U8, FDA Global Substance Registration System
• Retatrutide (sodium salt), PubChem CID 171934787, National Library of Medicine
• Li W et al., Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide, Cell Discovery, 2024
• Cao J et al., Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors, Nature Communications, 2025
• Pro-glucagon, human, UniProt P01275
• Gastric inhibitory polypeptide, human, UniProt P09681