Retatrutide vs tirzepatide vs semaglutide: structure

How the three molecules are built

	Semaglutide	Tirzepatide	Retatrutide
Backbone	GLP-1	GIP	GIP
Length	31 residues	39 residues	39 residues
Receptors	GLP-1R	GIPR, GLP-1R	GIPR, GLP-1R, GCGR
Non-coded residues	Substitution at GLP-1 position 8, against DPP-4	Aib at 2 and 13	Aib at 2 and 20, α-methyl-L-leucine at 13
Lipid chain	C18 fatty diacid and spacer on lysine 26 (GLP-1 numbering)	C20 fatty diacid through a linker on lysine 20	C20 fatty diacid through a linker on lysine 17
Molecular formula	C187H291N45O59	C225H348N48O68	C221H342N46O68
Molecular weight	4,113.58 (label)	4,813.53 (label)	4,731 (PubChem)
FDA status, October 13, 2026	Approved	Approved	Investigational

The semaglutide and tirzepatide columns are taken from the Description and Mechanism of Action sections of their FDA labels; the retatrutide column from PubChem and the 2024 structural study of retatrutide at its three receptors. The table of research materials and their certificates follows further down.

Retatrutide vs tirzepatide

These are the two closest in structure. Both are 39 residues long, both were developed from the GIP sequence, and both open with tyrosine followed by aminoisobutyric acid. Both carry a fatty diacid on a lysine to bind albumin.

They differ in several ways along the chain; four matter most. Retatrutide also activates the glucagon receptor, which tirzepatide does not. At position 13 tirzepatide has aminoisobutyric acid where retatrutide has α-methyl-L-leucine, and retatrutide carries a second Aib at position 20. The lipid sits on lysine 20 in tirzepatide and on lysine 17 in retatrutide. And the molecular weights differ by 82, 4,813 against 4,731, which is the quickest way to tell the materials apart on a mass spectrum. Tirzepatide is approved as Mounjaro (May 13, 2022) and Zepbound (November 8, 2023); retatrutide is not approved.

Retatrutide vs semaglutide

These are further apart. Semaglutide is a GLP-1 analogue of 31 residues with 94 percent sequence homology to human GLP-1, according to its label, and it acts at the GLP-1 receptor only. Retatrutide is GIP-based, eight residues longer and active at three receptors. Both are lipidated, semaglutide with a C18 fatty diacid on lysine 26 counted in GLP-1's own numbering. The molecular weights differ by more than 600. Semaglutide is approved, as Ozempic, Wegovy and Rybelsus; retatrutide is not.

Telling the three apart on a certificate

Identity by mass spectrometry separates all three at once: 4,114, 4,813 and 4,731 are far enough apart that no working instrument confuses them. Purity by HPLC does not, because a purity figure says nothing about which peptide the main peak is. How to read a retatrutide certificate goes through each line, retatrutide structure and receptors explains where the mass difference comes from, and the retatrutide research reference lists every certificate on file.

What this comparison leaves out

Most of what search engines show for these three names is about outcomes in trials. This page does not compare them, and no page on this site does: they are not research questions about the materials, and a research supplier that quotes a sponsor's trial figures risks representing its product as the sponsor's drug. Where each molecule stands with the FDA is dated in retatrutide's FDA status and in what ended for compounded semaglutide and tirzepatide.

Research materials and certificates

	Semaglutide	Tirzepatide	Retatrutide
Also known as	None listed	LY-3298176	LY-3437943
Catalogue shelf	GLP-1 and metabolic	GLP-1 and metabolic	GLP-1 and metabolic
CAS number	910463-68-2	2023788-19-2	2381089-83-2
Molecular formula	C187H291N45O59	C225H348N48O68	C221H342N46O68
Molecular weight	4,114 g/mol	4,813 g/mol	4,731 g/mol
Chain length	31 residues	39 residues	39 residues
Form as supplied	Lyophilized powder	Lyophilized powder	Lyophilized powder
Storage	-20 °C, desiccated	-20 °C, desiccated	-20 °C, desiccated
Sizes stocked	5 mg, 10 mg, 20 mg, 30 mg, 50 mg	10 mg, 20 mg, 30 mg, 60 mg, 100 mg	10 mg, 20 mg, 30 mg, 48 mg, 60 mg, 200 mg
Current certificates	5 mg: 99.75%, lot SEMA5-0803 10 mg: 99.9%, lot SEMA10-0616 20 mg: 99.9%, lot SEMA20-0528 30 mg: 99.87%, lot SEMA30-0803	10 mg: 99.80%, lot TIR10-0803 20 mg: 99.80%, lot TIR20-0803 30 mg: 99.85%, lot TIR30-0803 60 mg: 99.79%, lot TIR60-0803 100 mg: 99.85%, lot TIR100-0803	20 mg: 99.79%, lot RETA20-0803 30 mg: 99.83%, lot RETA30-0803 48 mg: 99.9%, lot RETA48-0616 60 mg: 99.85%, lot RETA60-0803
PubChem record	CID 56843331	CID 156588324	CID 171934787

Figures are the ones printed on each product page. Purity appears only where a current laboratory certificate supports it, and links to that certificate.

Common questions

What is the structural difference between retatrutide and tirzepatide?

Both are 39-residue GIP-based peptides with a fatty diacid on a lysine. Retatrutide has α-methyl-L-leucine at position 13 where tirzepatide has aminoisobutyric acid, a second aminoisobutyric acid at position 20, and its lipid on lysine 17 rather than 20. It also activates the glucagon receptor, and it is 82 lighter: 4,731 against 4,813.

How is retatrutide different from semaglutide?

Semaglutide is a 31-residue GLP-1 analogue that acts at the GLP-1 receptor only. Retatrutide is a 39-residue GIP-based peptide that acts at the GIP, GLP-1 and glucagon receptors. Semaglutide is FDA-approved; retatrutide is investigational.

Which of the three are FDA approved?

As of October 13, 2026, semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) are FDA-approved. Retatrutide is investigational, with no approved product.

Why do retatrutide and tirzepatide have the same length?

Both are 39-residue designs that start from GIP’s sequence, so both open with tyrosine, and both replace the second residue with aminoisobutyric acid. They differ in substitutions along the chain, the position of the lipid and the receptors they reach.

Retatrutide vs tirzepatide vs semaglutide