Amycretin (Unimolecular Amylin-GLP-1 Co-Agonist) — Weight & Metabolism
Investigational single-molecule co-agonist activating both amylin and GLP-1 receptors, with both oral and injectable formulations in Phase 3 development.
Overview
Amycretin is a first-in-class unimolecular co-agonist that activates both amylin and GLP-1 receptors from a single peptide molecule, developed by Novo Nordisk and currently in Phase 3 clinical trials. Unlike CagriSema (which combines two separate molecules), amycretin integrates both receptor-binding domains into one molecule for potentially simplified manufacturing and dosing. Phase 2 data for the oral formulation demonstrated approximately 22% body weight loss at 36 weeks, making it the most effective oral obesity treatment reported to date. The injectable formulation has also shown impressive early-phase results. Phase 2 data showed oral amycretin achieved weight loss comparable to or exceeding injectable semaglutide 2.4mg, a breakthrough for oral peptide delivery. The dual amylin-GLP-1 mechanism provides complementary appetite suppression through both hindbrain (amylin) and hypothalamic (GLP-1) pathways. Phase 3 trials are underway for both oral and subcutaneous formulations. Novo Nordisk has positioned amycretin as a potential next-generation obesity treatment.
Indications
- Obesity (BMI >=30) or overweight (BMI >=27) with comorbidities (Phase 3 - oral and injectable)
- Type 2 diabetes with obesity (anticipated indication based on dual mechanism)
- Patients preferring oral over injectable obesity medication (oral formulation in development)
Mechanism of Action
Insufficient amylin and GLP-1 signaling contributes to excess appetite, poor satiety, and metabolic dysfunction
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Amycretin (oral) | Titrated to target dose | Once daily (fasting) | Oral formulation achieved ~22% weight loss at 36 weeks in Phase 2; take on empty stomach |
| Amycretin (injectable) | Titrated to target dose | Once weekly | Injectable formulation also in development; specific doses not yet publicly disclosed |
Evidence Grade
GRADE D
Safety & Contraindications
- Investigational compound - NOT FDA-approved; Phase 3 trials recently initiated
- GI side effects expected: nausea, vomiting, diarrhea consistent with GLP-1 and amylin class effects
- Oral formulation requires fasting conditions for absorption (similar to oral semaglutide)
- Limited long-term safety data available; Phase 2 data suggests manageable adverse event profile
- Dual receptor activation may produce different safety signals than single-target agents - monitoring ongoing
- No head-to-head data vs CagriSema yet; comparative safety/efficacy to be determined in future trials