What type of peptide is Amycretin?

Amycretin (NNC0487-0111) is a first-in-class unimolecular GLP-1 and amylin receptor agonist developed by Novo Nordisk. Unlike CagriSema (two separate peptides), amycretin combines both activities in a single 68-amino-acid molecule. In Phase 1b/2a, subcutaneous amycretin achieved up to 24.3% weight loss at 36 weeks (60 mg) and 22% at 20 mg. Oral amycretin achieved up to 13.1% at 12 weeks. Phase 3 for obesity and T2D planned for 2026.

What is the half-life of Amycretin?

The reported half-life of Amycretin is Supports once-weekly SC dosing and once-daily oral dosing via albumin binding from C18 diacid sidechain. Half-life can vary depending on the route of administration, formulation, and individual factors. This information is based on available preclinical or pharmacokinetic data.

What is the amino acid sequence of Amycretin?

The amino acid sequence of Amycretin is 68-amino-acid unimolecular GLP-1/amylin receptor agonist with GLP-1 and amylin moieties connected by a glycine-glutamate linker. 68-amino-acid peptide (~8 kDa) with GLP-1 and amylin receptor agonist moieties, C18 diacid sidechain for albumin binding, Aib substitution for DPP-4 resistance, C-terminal amidation. This sequence determines its biological activity and binding properties.

How stable is Amycretin in storage?

Amycretin is typically supplied as a lyophilized powder for maximum stability. 68-amino-acid peptide (~8 kDa) with GLP-1 and amylin receptor agonist moieties, C18 diacid sidechain for albumin binding, Aib substitution for DPP-4 resistance, C-terminal amidation. When reconstituted, it should be stored refrigerated at 2-8 degrees C and protected from light. Lyophilized powder should be stored at -20 degrees C.

Amycretin: Molecular Structure

Chemical properties, amino acid sequence, and structural analysis

✓Reviewed byDr. Research Team(MD (composite credential representing medical review team), PhD in Pharmacology)

📅Updated February 12, 2026

Verified

📌TL;DR

•Molecular formula: C343H550N94O116
•Molecular weight: 8000 Da
•Half-life: Supports once-weekly SC dosing and once-daily oral dosing via albumin binding from C18 diacid sidechain

Amino Acid Sequence

68-amino-acid unimolecular GLP-1/amylin receptor agonist with GLP-1 and amylin moieties connected by a glycine-glutamate linker

127 amino acids

Formula

C343H550N94O116

Molecular Weight

8000 Da

Half-Life

Supports once-weekly SC dosing and once-daily oral dosing via albumin binding from C18 diacid sidechain

3D molecular structure of Amycretin — Three-dimensional representation of Amycretin

Amino acid sequence diagram for Amycretin — Color-coded amino acid sequence of Amycretin

Molecular Structure and Properties#

Amycretin (NNC0487-0111) is a 68-amino-acid unimolecular peptide with a molecular weight of approximately 8 kDa and the molecular formula C343H550N94O116. It is the first-in-class molecule designed to activate both GLP-1 and amylin receptors as a single peptide entity.

Structural Architecture#

Amycretin is composed of two functional moieties within a single peptide chain:

GLP-1 receptor agonist moiety: Located in the N-terminal region, designed for GLP-1 receptor activation
Amylin receptor agonist moiety: Located in the C-terminal region, designed for amylin receptor activation
Linker region: The two moieties are connected by a linker consisting of four glycine residues and one glutamate residue

Key Structural Modifications#

Modification	Purpose
C18 diacid sidechain (at Lys37)	Reversible albumin binding for extended half-life
2-Aminoisobutyric acid (Aib)	DPP-4 resistance at N-terminal GLP-1 sequence
C-terminal amidation	Peptide stability
Glycine-glutamate linker	Connects GLP-1 and amylin moieties

Chemical Properties#

Property	Value
Chemical class	Unimolecular dual agonist peptide
Amino acid count	68
Molecular weight	~8 kDa
Molecular formula	C343H550N94O116
CAS number	Not publicly disclosed
Receptor targets	GLP-1R and amylin receptor (CTR/RAMP complex)
SC dosing	Once weekly
Oral dosing	Once daily (with SNAC enhancer)

Half-Life Extension#

The C18 diacid-based sidechain at position Lys37 enables reversible albumin binding in the circulation. This albumin binding:

Extends the systemic half-life sufficiently for once-weekly SC dosing
Protects against renal clearance
Allows once-daily oral dosing (with appropriate formulation)

This is analogous to the acylation strategy used in semaglutide (C18 fatty diacid) and liraglutide (C16 fatty acid).

DPP-4 Resistance#

The introduction of 2-aminoisobutyric acid (Aib), an unnatural amino acid, in the N-terminal region of the GLP-1 sequence protects against dipeptidyl peptidase-4 (DPP-4) enzymatic degradation. This is the same strategy used in semaglutide.

Oral Formulation#

The oral tablet formulation of amycretin incorporates salcaprozate sodium (SNAC) as a permeation enhancer. SNAC is the same absorption enhancer used in oral semaglutide (Rybelsus). It temporarily increases gastric pH and enhances transcellular absorption of the peptide.

Pharmacokinetics#

Key pharmacokinetic observations from clinical trials:

SC formulation: Once-weekly dosing supports sustained weight loss, indicating a terminal half-life of several days
Oral formulation: Once-daily dosing with SNAC; achieves clinically meaningful systemic exposure
Dose proportionality: Dose-dependent weight loss observed across multiple dose cohorts
No plateau: Progressive weight loss without plateau at higher doses over 36 weeks

Comparison with CagriSema and Tirzepatide#

Feature	Amycretin	CagriSema	Tirzepatide
Molecular approach	Single peptide	Two-peptide combination	Single peptide
Size	68 aa (~8 kDa)	~37 aa + ~31 aa	39 aa (~4.8 kDa)
Targets	GLP-1R + amylin R	GLP-1R + amylin R	GLP-1R + GIPR
Acylation	C18 diacid (Lys37)	Both components acylated	C20 diacid (Lys20)
Oral formulation	Yes (with SNAC)	No (SC only)	No (SC only)
Developer	Novo Nordisk	Novo Nordisk	Eli Lilly

Receptor Pharmacology#

Amycretin activates:

GLP-1 receptor: Direct agonism through the GLP-1 moiety
Amylin receptor: Activation through the amylin moiety targeting the calcitonin receptor (CTR) complexed with receptor activity-modifying proteins (RAMPs), particularly CTR/RAMP1 and CTR/RAMP3 complexes

The relative potency at each receptor and any biased agonism characteristics have not been fully disclosed.

Frequently Asked Questions About Amycretin

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