Amycretin
InvestigationalAlso known as: NNC0487-0111, Oral Amycretin, Subcutaneous Amycretin
A novel single-molecule dual GLP-1/amylin receptor agonist developed by Novo Nordisk. Unlike CagriSema (a fixed-dose combination), amycretin is a unified peptide that activates both pathways. Phase 1 trials showed superior weight loss signals versus semaglutide, with both oral and subcutaneous formulations in development.
Research Statistics
Novo Nordisk Phase 2 dual amylin/GLP-1 agonist; early but promising; limited to one company.
Research Dossier
Overview
What is Amycretin and what does the research say?
Mechanism of Action
The proposed mechanisms of amycretin are based on Phase 1 clinical data and extensive preclinical validation of the dual GLP-1/amylin pathway approach.
How It Works (Simplified)
Amycretin is a single molecule designed to activate two appetite-control systems simultaneously:
Activates GLP-1 receptors in hypothalamus for appetite suppression and pancreas for glucose-dependent insulin release, like semaglutide.
Activates amylin receptors in brainstem (area postrema) providing a second, independent satiety signal through different neural circuits.
Amylin pathway restores responsiveness to leptin in obesity, a mechanism not achieved by GLP-1 agonists alone.
Engineered for oral delivery using absorption enhancer technology, enabling once-daily pill format versus weekly injections.
Scientific Pathways
GLP-1 Pathway (Hypothalamic Satiety)
Amycretin → GLP-1R activation → POMC/CART neurons → Satiety signal
→ NPY/AgRP inhibition → Reduced hunger
→ Pancreatic beta cells → Insulin secretionAmylin Pathway (Brainstem Satiety)
Amycretin → AMY1/AMY3 receptors → Area postrema activation → Meal termination
→ Leptin sensitization → Enhanced satietyKey Research: Roth JD et al. (2008) demonstrated amylin restores leptin sensitivity in obesity. PMID:18458326
Important Limitations
- Phase 1 data only; no Phase 2 or Phase 3 results yet
- All efficacy figures from company investor presentations, not peer-reviewed publications
- Clinical trial NCT identifiers not publicly disclosed
- Long-term safety beyond 36 weeks not established
- Head-to-head comparisons with semaglutide/tirzepatide are indirect only
- Molecular structure and sequence not publicly available
Evidence-Chained Benefits
Evidence-Chained Benefits
Research findings linked to mechanisms and clinical outcomes
What to Expect
Timeline based on observations from published studies. Individual responses may vary.
Based on GLP-1/amylin class effects: Initial appetite suppression and reduced food intake. GI side effects (nausea, reduced appetite) most common during this period. Weight loss begins, typically 2-4% in first month.
Phase 1 oral data: ~13% weight loss achieved by week 12. Progressive weight reduction as dose escalation completes. GI tolerability typically improves after initial weeks.
Continued weight loss trajectory. Based on SC Phase 1 data, weight loss continues beyond week 12. Metabolic improvements (if diabetic) would be expected based on class effects.
SC Phase 1 achieved up to ~22% weight loss at 36 weeks. Weight loss may begin plateauing at higher doses. Long-term tolerance and adherence not yet characterized.
Research-Based Observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Quality Checklist
Visual indicators to help evaluate Amycretin product quality
Good Signs (4 indicators)
Warning Signs (3 indicators)
Bad Signs (4 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Peptide Interactions
Known and theoretical interactions when combining Amycretin with other peptides. Based on published research and mechanistic considerations.
Semaglutide
CautionBoth are GLP-1 receptor agonists. Combining would result in overlapping mechanisms with potential for additive GI side effects. Not intended for concurrent use.
Tirzepatide
CautionBoth target GLP-1 receptor with additional mechanisms. Concurrent use would provide overlapping GLP-1 activity. Not recommended for combination.
Liraglutide
CautionBoth are GLP-1 receptor agonists. Overlapping mechanisms would not provide additive benefit and may increase adverse event risk.
Cagrisema
AvoidCagriSema contains both GLP-1 and amylin agonist components. Amycretin duplicates this dual mechanism in a single molecule. Combination would be redundant and potentially unsafe.
Cagrilintide
AvoidAmycretin already incorporates amylin receptor agonism. Adding cagrilintide would duplicate the amylin pathway with no expected additional benefit.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
References
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
Methodology Note
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
Get Research Alerts
New dossiers and major study summaries delivered to your inbox. Evidence-graded, citation-backed research you can trust.
No spam. Unsubscribe anytime.
Compare Amycretin
Related Peptides
5-Amino-1MQ
5-Amino-1-Methylquinolinium, NNMT Inhibitor
A small molecule NNMT inhibitor studied for metabolic effects in animal models. No human clinical trials have been conducted. Increases NAD+ levels in adipose tissue in preclinical studies.
AOD-9604
Anti-Obesity Drug 9604, Tyr-hGH Fragment 177-191, hGH Fragment 176-191
A modified fragment of human growth hormone (amino acids 176-191 with N-terminal tyrosine) studied for fat loss. Clinical development discontinued after Phase 2b/3 trials failed to show efficacy in 536 subjects. Now prohibited by WADA and excluded from FDA compounding.
Cagrilintide
AM833, NN9838, ZP8396
A long-acting amylin analog developed by Novo Nordisk for weight management. Currently in Phase 3 trials as CagriSema (combination with semaglutide). Phase 2 data shows up to 22-25% weight loss when combined with semaglutide, potentially exceeding tirzepatide efficacy.
CT-388
RG-6912
A dual GLP-1/GIP receptor agonist acquired by Roche through the $2.7 billion Carmot Therapeutics acquisition in 2024. Phase 1b results showed 18.8% placebo-adjusted weight loss at 24 weeks, positioning it as a competitive obesity therapeutic with a mechanism similar to tirzepatide.
Liraglutide
Victoza, Saxenda, NN2211
The first long-acting GLP-1 receptor agonist, FDA-approved for type 2 diabetes (Victoza, 2010) and chronic weight management (Saxenda, 2014). Pioneered the therapeutic class with proven cardiovascular benefits in the landmark LEADER trial.
MariTide
AMG 133, maridebart cafraglutide
A bispecific peptide-antibody conjugate combining GLP-1 receptor agonism with GIP receptor antagonism. Unique mechanism opposite to tirzepatide. Phase 2 showed ~20% weight loss at 52 weeks with once-monthly dosing. MARITIME Phase 3 program initiated.