Avexitide
Also known as: Exendin(9-39), EXE-9-39, AMX0114 (legacy code)
Overview
Avexitide is an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist derived from exendin(9-39), a 31-amino-acid truncated fragment of exendin-4 (the parent peptide of exenatide). Removing the first eight residues converts the agonist into a competitive antagonist at the GLP-1 receptor. Avexitide is being developed by Amylyx Pharmaceuticals (NASDAQ: AMLX) for post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass. The pivotal Phase 3 LUCIDITY trial (NCT06747468) completed enrollment in March 2026 with 78 participants; topline results are expected in Q3 2026. The drug holds FDA Breakthrough Therapy Designation for both PBH and congenital hyperinsulinism, Orphan Drug Designation for hyperinsulinemic hypoglycemia, and Rare Pediatric Disease Designation for congenital HI.
Mechanism of Action
Avexitide binds the GLP-1 receptor (GLP-1R) on pancreatic islet beta cells and acts as a competitive antagonist, blocking endogenous GLP-1 from coupling the receptor to its downstream Gs/cAMP/PKA cascade. In post-bariatric hypoglycemia, surgical rerouting of the gastrointestinal tract delivers nutrients to distal L-cells faster than in an unaltered gut, producing an exaggerated postprandial GLP-1 surge that drives excessive glucose-dependent insulin secretion and a delayed but severe drop in blood glucose. By antagonizing the receptor, avexitide blunts the inappropriate insulin spike while preserving baseline glucose homeostasis. The molecule does not address GLP-1 effects on gastric emptying or central satiety to a degree that would induce hypoglycemia recovery side effects.
Potential Benefits
- First-in-class therapeutic strategy for post-bariatric hypoglycemia
- 53% reduction in Level 2 hypoglycemia events in Phase 2b at 90 mg dose (p=0.004)
- 66% reduction in Level 3 hypoglycemia events in Phase 2b at 90 mg dose (p=0.0003)
- Generally well-tolerated across five Phase 1 and Phase 2 trials
- Targets the underlying pathology (excessive GLP-1 signal) rather than symptoms
- Subcutaneous once-daily dosing
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Beginner | Not applicable; investigational use only via clinical trial or Expanded Access Program |
| Intermediate | Not applicable; investigational use only |
| Advanced | Not applicable; investigational use only |
| Cycle Duration | 16 weeks double-blind in Phase 3, 32-week open-label extension |
Avexitide is investigational. Access is limited to enrolled patients in LUCIDITY (now closed to enrollment) and adults with PBH following RYGB who qualify for the Amylyx Expanded Access Program.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Subcutaneous Injection Investigational; not publicly disclosed for avexitide formulation
Once-daily subcutaneous administration in LUCIDITY Phase 3.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Reconstitution
| Storage | Per Amylyx investigational product handling guidelines provided to clinical trial sites |
|---|
Reconstitution and storage details available only to clinical trial sites and Expanded Access Program participants.
Need exact syringe measurements?
Amino Acid Sequence
31-amino-acid peptide derived from exendin(9-39); truncated form of the 39-amino-acid exendin-4 with N-terminal residues 1-8 removed (converts agonist to antagonist)
Side Effects & Safety
- Generally well-tolerated across clinical trials per sponsor reports
- Injection site reactions (subcutaneous administration)
- Detailed Phase 3 safety profile pending Q3 2026 readout
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Use Outside the Indicated Population
Pregnancy / Lactation
Drug Interactions
- GLP-1 Receptor Agonists (semaglutide, tirzepatide, liraglutide, dulaglutide, exenatide):
FDA Safety Information
Investigational; full FDA safety labeling pending review of Phase 3 LUCIDITY data anticipated Q3 2026.
Pharmacokinetics
| Half-Life | Short half-life consistent with the parent exendin(9-39) fragment; once-daily 90 mg subcutaneous dosing provides therapeutic exposure across the postprandial window in PBH patients |
|---|---|
| Storage | Investigational product; storage per sponsor instructions |
Synergistic Compounds
The following compounds have been studied alongside Avexitide for potential complementary or synergistic effects:
Learn More
References & Further Reading
- ClinicalTrials.gov NCT06747468 - Avexitide for Treatment of Post-Bariatric Hypoglycemia (LUCIDITY)
- Amylyx Announces U.S. Expanded Access Program for Avexitide (May 5, 2026)
- Amylyx Announces Completion of Enrollment in Pivotal Phase 3 LUCIDITY Trial
- Amylyx Announces Pivotal Phase 3 LUCIDITY Trial Design
- Amylyx Q1 2026 Financial Results (May 7, 2026)
Latest News & Research
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Avexitide expanded access opens: a GLP-1 receptor antagonist heads to its Phase 3 readout
Amylyx opens U.S. expanded access for up to 250 PBH patients on avexitide, the first-in-class GLP-1 antagonist; LUCIDITY Phase 3 readout due Q3 2026 data.
FDA's second PCAC peptide review: the 5 substances heading to a Feb 2027 meeting
FDA confirms a second PCAC meeting before end of February 2027 will review LL-37, injectable GHK-Cu, Dihexa, Melanotan II, and PEG-MGF for the 503A list.
Ozempic-branded oral semaglutide hits US pharmacies with primary + secondary CV indication
Novo Nordisk's oral semaglutide launches as Ozempic tablets on May 4 with a primary + secondary CV prevention label, on the strength of the SOUL trial.
Semaglutide beats dulaglutide on MACE in 75,243-patient Medicare comparison
A 75,243-patient Medicare propensity-matched study finds once-weekly semaglutide cut three-point MACE 22% versus dulaglutide in older type 2 diabetes adults.