Amycretin
Also known as: NN9487, Unimolecular GLP-1/amylin receptor agonist, NNC0174-0987
Overview
Amycretin is a novel, unimolecular long-acting dual agonist of both the GLP-1 and amylin receptors, developed by Novo Nordisk as a next-generation obesity and type 2 diabetes treatment. Unlike CagriSema (a fixed-dose combination of two separate molecules), amycretin is engineered as a single molecule that simultaneously activates both receptor systems, potentially offering pharmacokinetic and compliance advantages. Phase 1b/2a results published in The Lancet (June 2025) showed up to 22% weight loss at 36 weeks for the injectable 20 mg dose and 13.1% for the 100 mg/day oral dose in people with overweight or obesity — all without an observed weight-loss plateau. Phase 2 data in type 2 diabetes (November 2025) showed up to 14.5% weight loss and 1.8% HbA1c reduction at 36 weeks with the subcutaneous formulation. Both the subcutaneous and oral formulations are advancing directly to Phase 3 development starting in 2026, targeting obesity and type 2 diabetes.
Mechanism of Action
Amycretin simultaneously activates GLP-1 receptors (appetite suppression, insulin secretion, glucose lowering) and amylin receptors (postprandial glucagon suppression, gastric emptying delay, additional hypothalamic satiety signaling) as a single unimolecular agent. This dual mechanism is synergistic: the amylin pathway provides additional appetite control independent of GLP-1, explaining superior weight loss versus GLP-1 monotherapy. No weight-loss plateau was observed at 36 weeks in either obesity or T2D trials.
Potential Benefits
- Up to 22% weight loss at 36 weeks (subcutaneous 20 mg, Phase 1b/2a obesity trial)
- Up to 24.3% weight loss at 36 weeks (subcutaneous 60 mg, escalation cohort)
- 13.1% weight loss at 12 weeks with oral formulation (100 mg/day)
- 14.5% weight loss at 36 weeks in T2D patients (SC formulation, Phase 2)
- 10.1% weight loss at 36 weeks in T2D patients (oral formulation)
- Up to 1.8% HbA1c reduction in T2D (SC), 1.5% (oral)
- No weight-loss plateau observed at 36 weeks across formulations
- Dual GLP-1/amylin mechanism provides additive weight loss vs. GLP-1 alone
- Available in both injectable (once-weekly) and oral (once-daily) formulations
Research Dosage Notes
The following reflects doses used in published research studies. This is not medical advice.
Consult published research literature for study-specific protocols.
Routes of Administration
Subcutaneous Injection High
Once-weekly SC injection; Phase 1b/2a: 125 adults, 36 weeks, doses 0.3–60 mg; NCT06064006. Phase 2 T2D: NCT06542874, doses 0.4–40 mg over 36 weeks.
Oral Low-moderate (absorption enhancer formulation)
Once-daily oral; Phase 1: 144 adults, 12 weeks, doses up to 2x50 mg/day. 13.1% weight loss at 12 weeks (100 mg/day). GI tolerability a key concern (37.5% vomiting at higher doses in Phase 1).
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving Amycretin:
Metabolic Health Stack
Combines Amycretin with MOTS-c (mitochondrial metabolism) and AOD-9604 (lipolysis) for metabolic optimization.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Storage | Refrigerate at 2-8°C after reconstitution. Do not freeze reconstituted solution. |
|---|
Typical vial sizes: 5 mg. Add bac water slowly down the side of the vial, swirl gently — do not shake. Use insulin syringe for precise dosing.
Need exact syringe measurements?
Amino Acid Sequence
Proprietary Novo Nordisk unimolecular structure; engineered to activate GLP-1R and amylin receptors with fatty acid modification for extended half-life
Side Effects & Safety
- Nausea (most common; dose-dependent, typically mild to moderate)
- Vomiting (37.5% rate in oral Phase 1 at higher doses — key tolerability concern)
- Decreased appetite (intended therapeutic effect)
- Diarrhea (GLP-1 class effect)
- Constipation
- Gastrointestinal events were the primary TEAEs; majority resolved by end of study
- Higher rates of GI events with oral vs. SC formulation at equivalent efficacy
- No new safety signals beyond GLP-1/amylin class effects
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
MTC/MEN2
GLP-1 receptor agonists carry a boxed warning for medullary thyroid carcinoma (MTC) risk. Contraindicated in patients with personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN2).
Severe Gastroparesis
GLP-1/amylin dual agonism may significantly delay gastric emptying. Use with caution in patients with pre-existing severe gastroparesis.
Pancreatitis History
GLP-1 agonists have been associated with acute pancreatitis. Discontinue if pancreatitis is suspected.
Pregnancy & Lactation
No human data available. Discontinue at least 2 months before planned conception.
Drug Interactions
- Oral medications: May delay absorption of oral medications due to slowed gastric emptying. Take time-sensitive medications (e.g., oral contraceptives, antibiotics) at least 1 hour before amycretin.
- Insulin/sulfonylureas: Increased risk of hypoglycemia when combined with insulin or insulin secretagogues. Dose reduction may be needed.
Pharmacokinetics
| Half-Life | ~7 days (once-weekly SC dosing compatible; similar to semaglutide through fatty acid modification) |
|---|---|
| Storage | Refrigerate at 2–8°C; do not freeze; clinical formulation in pre-filled pen/device |
Synergistic Compounds
The following compounds have been studied alongside Amycretin for potential complementary or synergistic effects:
Learn More
References & Further Reading
- Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study
- PubMed: Amycretin phase 1b/2a subcutaneous trial
- Novo Nordisk advances amycretin to Phase 3 development based on early-phase results
- Novo Nordisk to advance amylin agonist to Phase III in type 2 diabetes
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