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CagriSema's two mechanisms in one molecule — and one of the few incretin-class peptides with an oral formulation in trials.
Also known as: NN9487 · NNC0487-0111 · GLP-1 / amylin co-agonist
Part of the Metabolic & GLP-1 peptides cluster
Overview
Amycretin (NN9487) is an investigational Novo Nordisk peptide that activates both the GLP-1 receptor and amylin receptors from a single chain — the same two mechanisms CagriSema delivers with two separate peptides. In phase 1b/2a, once-weekly subcutaneous amycretin produced up to −24.3% body weight at 36 weeks; an oral formulation is also in development. Its sequence has not been published.
Source & context
Biological / chemical source: Synthetic engineered peptide (full sequence not publicly disclosed)
Primary research or clinical context: Investigational (Novo Nordisk) — once-weekly subcutaneous and once-daily oral formulations in clinical trials; not approved as of September 2026
What amycretin is
Amycretin is a single peptide engineered to do what CagriSema does with two: activate the GLP-1 receptor and the amylin receptors at the same time. Novo Nordisk developed it as a successor to the cagrilintide–semaglutide combination, with the practical advantages that one molecule is simpler to manufacture and formulate, and that it can be made as an oral tablet as well as a weekly injection. The company has not published the sequence, so this profile cannot give the residue-level detail available for semaglutide or tirzepatide.
Two receptors in one chain
GLP-1 and amylin reduce appetite through partly separate neural pathways and have different side-effect signatures, which is why combining them produced more weight loss than either alone in REDEFINE 1. Doing it in one molecule requires a sequence that both receptor families recognise — a harder design problem than the GIP/GLP-1 dual agonists, because amylin receptors are calcitonin-receptor complexes structurally unrelated to the GLP-1 receptor. Amycretin's existence shows it can be done; how the balance is tuned has not been disclosed.
Phase 1 results: subcutaneous and oral
Two Lancet papers in 2025 reported the first human data. In the subcutaneous phase 1b/2a study (125 adults with overweight or obesity), once-weekly amycretin produced mean weight changes of −24.3% at 36 weeks on 60 mg (placebo −1.1%), −22.0% on 20 mg at 36 weeks, −16.2% on 5 mg at 28 weeks and −9.7% on 1.25 mg at 20 weeks. Gastrointestinal adverse events were the most common and mostly mild to moderate, though a large number of participants withdrew, many for reasons unrelated to adverse events. The oral formulation's first-in-human study also reported dose-proportional exposure and weight loss.
| Dose | Duration | Amycretin | Placebo |
|---|---|---|---|
| 1.25 mg weekly | 20 weeks | −9.7% | +2.0% |
| 5 mg weekly | 28 weeks | −16.2% | +2.3% |
| 20 mg weekly | 36 weeks | −22.0% | +1.9% |
| 60 mg weekly | 36 weeks | −24.3% | −1.1% |
Amycretin vs CagriSema
CagriSema pairs cagrilintide 2.4 mg with semaglutide 2.4 mg and reached −20.4% at 68 weeks in phase 3. Amycretin reached −24.3% at 36 weeks in a small phase 1b/2a study — a shorter trial with far fewer participants, so the numbers are not comparable. The strategic difference is that amycretin is one molecule with an oral option, while CagriSema is two established peptides in one pen and is closer to approval.
Status
Amycretin is investigational. Novo Nordisk has moved it into later-phase trials following the 2025 publications; as of September 2026 it is not approved anywhere and no pharmaceutical product exists outside trials. Nothing sold online under the name can be verified against a published structure, since none has been released.
Structure & chemistry
Molecular identity & reference confidence
Reference mass unavailable
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Not disclosed; described by Novo Nordisk as a single engineered peptide
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- Plasma half-life
- Supports once-weekly subcutaneous dosing; the oral formulation is dosed once daily
- Receptors
- GLP-1 receptor and amylin receptors (calcitonin receptor + RAMP complexes) — a unimolecular co-agonist
- Backbone
- Not disclosed; described by Novo Nordisk as a single engineered peptide
- Status
- Investigational (phase 2 results published 2025; later-phase trials under way). Not approved as of September 2026
Chemistry values: curated profile.
Clinical development snapshot
ClinicalTrials.gov lists 1 registered study with “Amycretin” as an intervention (snapshot 2026-09-06). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT06049329 | A Research Study of How a New Medicine Called Amycretin, Given as Tablets, Works in Japanese Men With Obesity | Phase 1 | completed | 2025-03-05 |
The incretin & metabolic co-agonist class at a glance
| Peptide | Receptors | Length | Mass (Da) | Half-life | Status |
|---|---|---|---|---|---|
| GLP-1 | GLP-1R | 30 aa | ≈ 3,297.6 | ≈ 1–2 min (DPP-4 cleavage + renal clearance) | Endogenous hormone — not a product |
| Liraglutide | GLP-1R | 31 aa | ≈ 3,751.2 | ≈ 13 h (once-daily dosing) | Approved: Victoza (2010, T2D), Saxenda (2014, weight) |
| Semaglutide | GLP-1R | 31 aa | ≈ 4,113.6 | ≈ 7 days (≈ 145–165 h in clinical PK studies) | Approved: Ozempic (2017, T2D), Rybelsus (2019, oral T2D), Wegovy (2021, weight) |
| Tirzepatide | GIPR + GLP-1R | 39 aa | ≈ 4,813.5 | ≈ 5 days (≈ 117 h) | Approved: Mounjaro (2022, T2D), Zepbound (2023, weight; 2024, obstructive sleep apnoea) |
| Retatrutide | GIPR + GLP-1R + GCGR | 39 aa | ≈ 4,731 | ≈ 6 days | Investigational (phase 3) |
| Cagrilintide | Amylin / calcitonin | 37 aa | ≈ 4,409 | ≈ 7–8 days (159–195 h across doses in the phase 1b study) | Investigational (phase 3, as CagriSema with semaglutide) |
| Survodutide | GCGR + GLP-1R | 29 aa | ≈ 4,232 | Supports once-weekly dosing (published population estimates are on the order of several days) | Investigational (phase 3: SYNCHRONIZE obesity programme; MASH programme) |
| Mazdutide | GCGR + GLP-1R | 34 aa | ≈ 4,476 | Supports once-weekly dosing (published estimates are on the order of several days) | Approved in China (NMPA): chronic weight management (27 June 2025) and type 2 diabetes (2025) |
| Amycretin (this page) | GLP-1R + amylin | — | — | Supports once-weekly subcutaneous dosing | Investigational (phase 2 results published 2025; later-phase trials under way) |
Verified from PubChem, IUPHAR and the primary discovery papers cited on each profile. Half-lives are approximate population means from published pharmacokinetics.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Amycretin
What is Amycretin?+
Amycretin (NN9487) is an investigational Novo Nordisk peptide that activates both the GLP-1 receptor and amylin receptors from a single chain — the same two mechanisms CagriSema delivers with two separate peptides. In phase 1b/2a, once-weekly subcutaneous amycretin produced up to −24.3% body weight at 36 weeks; an oral formulation is also in development. Its sequence has not been published.
What Canadian product status is recorded for Amycretin?+
Canadian product status for Amycretin has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Amycretin?+
Amycretin is not a classic amino-acid chain peptide in the same sense; see the profile for classification details.
What is amycretin?+
An investigational Novo Nordisk peptide that activates both GLP-1 and amylin receptors from a single molecule. It is being developed as a once-weekly injection and as an oral tablet.
How much weight loss did amycretin produce?+
Up to −24.3% at 36 weeks on 60 mg weekly (versus −1.1% placebo) in a phase 1b/2a study of 125 adults. Larger, longer trials are under way.
Is amycretin the same as CagriSema?+
No. CagriSema is two separate peptides (cagrilintide and semaglutide) co-formulated; amycretin is one engineered peptide that hits both receptor types.
Is amycretin approved?+
No. As of September 2026 it is investigational and not approved in any country.
Further reading
- Metabolic peptidesCagriSema Explained: Cagrilintide + Semaglutide, Mechanism and REDEFINE Trial ResultsCagriSema combines cagrilintide (a long-acting amylin analogue) with semaglutide (a GLP-1 agonist) in one weekly injection. This guide explains why two receptors beat one, what REDEFINE 1 showed (−20.4% at 68 weeks), how it compares with tirzepatide and retatrutide, and where approval stands.
- Metabolic peptidesGLP-1 Peptides Explained: GLP-1, Semaglutide, Tirzepatide, RetatrutideFrom endogenous GLP-1 to dual and triple agonists—an educational map of incretin peptide science and metabolic drug design.
- ComparisonOrforglipron vs Peptide GLP-1 Agonists: Small Molecule vs Peptide, ExplainedOrforglipron (Foundayo, FDA-approved in the US in April 2026) is the first non-peptide GLP-1 receptor agonist. This guide explains how a small molecule activates a peptide receptor, why that allows a pill without food or water restrictions, how ATTAIN-1 results compare with semaglutide and tirzepatide trials, and what the trade-offs are.
Related peptides
References & further reading
- 1.Gasiorek et al. (2025). Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1 trial. Lancet 406(10499):135–148
- 2.Dahl et al. (2025). Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a trial in people with overweight or obesity. Lancet 406(10499):149–162
- 3.Novo Nordisk — R&D pipeline (amycretin, NN9487)