Tirzepatide vs semaglutide: the two molecules compared

The two molecules side by side

	Tirzepatide	Semaglutide
Backbone	GIP	GLP-1
Length	39 residues	31 residues
Receptors	GIP receptor and GLP-1 receptor	GLP-1 receptor
Non-coded residues	Aib at positions 2 and 13	Substitution at GLP-1 position 8, against DPP-4
Lipid chain	C20 fatty diacid through a linker on lysine 20	C18 fatty diacid and spacer on lysine 26 (GLP-1 numbering)
Molecular formula	C225H348N48O68	C187H291N45O59
Molecular weight (label)	4,813.53	4,113.58
Developer	Eli Lilly and Company	Novo Nordisk
Approved products	Mounjaro (2022), Zepbound (2023)	Ozempic (2017), Wegovy, Rybelsus

Both columns are taken from sections 11 and 12.1 of the FDA labels, Mounjaro for tirzepatide and Ozempic for semaglutide, with the tirzepatide linker from FDA's substance registry. The research materials and their certificates are tabled further down.

Where they differ

The backbone. Semaglutide is GLP-1 itself, modified: its label gives 94 percent sequence homology to human GLP-1. Tirzepatide's label describes it as "based on the GIP sequence", the other incretin hormone, and it acts at the GLP-1 receptor as well. It is eight residues longer.

The receptors. Semaglutide activates one receptor. Tirzepatide's label calls it "a GIP receptor and GLP-1 receptor agonist", and the 2022 cryo-EM structures show it bound to each.

The non-coded residues. Semaglutide's label describes a substitution at GLP-1 position 8 against the enzyme DPP-4. Tirzepatide's label gives aminoisobutyric acid at positions 2 and 13.

The lipid. Both bind albumin through a fatty diacid on a lysine. Semaglutide's is C18, on lysine 26 in GLP-1's own numbering; tirzepatide's is C20, on lysine 20.

Telling them apart on a certificate

Mass spectrometry separates them at once: about 4,114 against 4,814, a difference of 700. On an electrospray spectrum, tirzepatide's [M+4H]4+ ion sits near 1,204 and semaglutide's near 1,029. Purity by HPLC does not tell them apart, because a purity figure says nothing about which peptide the main peak is. How to read a tirzepatide certificate goes through each line, and the tirzepatide research reference lists every lot on file.

What this comparison leaves out

Most of what search engines show for "tirzepatide vs semaglutide" compares outcomes in trials. This page does not, and no page on this site does: those are not questions about the research materials, and a supplier quoting a sponsor's clinical figures risks representing its product as the sponsor's medicine. Where each stands with FDA is dated in is tirzepatide FDA approved? and, for compounding, in what ended for compounded semaglutide and tirzepatide.

Research materials and certificates

	Tirzepatide	Semaglutide
Also known as	LY-3298176	None listed
Catalogue shelf	GLP-1 and metabolic	GLP-1 and metabolic
CAS number	2023788-19-2	910463-68-2
Molecular formula	C225H348N48O68	C187H291N45O59
Molecular weight	4,813 g/mol	4,114 g/mol
Chain length	39 residues	31 residues
Form as supplied	Lyophilized powder	Lyophilized powder
Storage	-20 °C, desiccated	-20 °C, desiccated
Sizes stocked	10 mg, 20 mg, 30 mg, 60 mg, 100 mg	5 mg, 10 mg, 20 mg, 30 mg, 50 mg
Current certificates	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	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
PubChem record	CID 156588324	CID 56843331

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 tirzepatide and semaglutide?

Semaglutide is a 31-residue analogue of GLP-1 with a C18 fatty diacid on lysine 26. Tirzepatide is a 39-residue peptide built on GIP, with aminoisobutyric acid at positions 2 and 13, a C20 fatty diacid on lysine 20 and an amidated C-terminus.

Do tirzepatide and semaglutide act at the same receptors?

They share one. Semaglutide is a GLP-1 receptor agonist. Tirzepatide is an agonist at both the GLP-1 receptor and the GIP receptor.

Which is heavier, tirzepatide or semaglutide?

Tirzepatide, at 4,813.53 against 4,113.58 on their FDA labels. The 700-dalton gap is what separates them on a mass spectrum.

Are tirzepatide and semaglutide both FDA approved?

Both are active ingredients of FDA-approved products: tirzepatide in Mounjaro and Zepbound, semaglutide in Ozempic, Wegovy and Rybelsus. A research vial of either is not one of those products.

Tirzepatide vs semaglutide