---
title: "Trofinetide"
canonical_url: https://peptidelibrary.app/library/trofinetide
description: "FDA-approved treatment for Rett syndrome (Daybue, Daybue Stix) in adults and children aged 2 and older. A synthetic analog of a tripeptide from IGF-1, taken twice daily by weight, and its mechanism is unknown."
updated: 2026-10-30
publisher: Peptide Library
notice: "Research and educational use only. Not medical advice."
---

# Trofinetide

Trofinetide (also called Daybue or Daybue Stix) is an FDA-approved oral tripeptide analog for Rett syndrome. The FDA label says the way trofinetide works in Rett syndrome is unknown. It is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of IGF-1, with a methyl group on the proline that gave it a longer half-life and better oral absorption than the parent peptide.

FDA-approved treatment for Rett syndrome (Daybue, Daybue Stix) in adults and children aged 2 and older. A synthetic analog of a tripeptide from IGF-1, taken twice daily by weight, and its mechanism is unknown.

Also known as: Daybue, Daybue Stix, NNZ-2566.

Categories: Cognitive.

## Classification

- Type: FDA-approved oral tripeptide analog for Rett syndrome
- Mechanism class: IGF-1 Tripeptide Analog
- Development stage: Approved product
- Regulatory class: FDA-approved medicine

## Mechanism

The FDA label says the way trofinetide works in Rett syndrome is unknown. It is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of IGF-1, with a methyl group on the proline that gave it a longer half-life and better oral absorption than the parent peptide. In rodents, it reduced injury in a stroke model and corrected some deficits in a fragile X mouse model. Those findings do not establish how it acts in people.

Origin: Synthetic analog of Gly-Pro-Glu developed by Neuren Pharmaceuticals as NNZ-2566; the US product is from Acadia Pharmaceuticals.

## Properties

- Sequence: Gly-(2-methyl)Pro-Glu
- Molecular formula: C13H21N3O6
- Molecular weight: 315.33 g/mol
- CAS number: 853400-76-7
- Half-life: Effective half-life about 1.5 hours
- Studied routes: Oral, Gastrostomy tube

## Evidence

- Evidence level: FDA Approved
- Highest documented: Regulatory review (FDA label)
- Human trials: 7
- Controlled human trials: 4
- Preclinical sources: 1
- Latest source: 2025

Each step shows whether the sources Peptide Library has reviewed include that kind of research. Counts are reviewed sources, not every study ever published. Reviews and programme summaries that describe human use are shown as "reported", not as trials, and registered trials without published results are listed but not counted. A higher step means research has progressed further; it does not mean a compound works better or is safer. Compounds whose evidence has not been reviewed yet show "Not reviewed" instead of a guess.

### Studies

1. DAYBUE (trofinetide) oral solution and DAYBUE STIX for oral solution — FDA prescribing information, DailyMed. Regulatory label (FDA), human. Population: Adults and children aged 2 and older with Rett syndrome. Treatment of Rett syndrome [Source](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67e6f2d9-21f6-466f-9def-826c6a4b8257)
2. Neul JL et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med. 2023. 2023. Controlled human trial. Population: Girls and women aged 5 to 20 with Rett syndrome and a MECP2 mutation (93 on trofinetide, 94 on placebo). RSBQ score improved by 4.9 points versus 1.7 on placebo; CGI-I at week 12 was 3.5 versus 3.8 [Source](https://pubmed.ncbi.nlm.nih.gov/37291210/)
3. Percy AK et al. Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study. Med. 2024. 2024. Human study (early or uncontrolled). Population: Girls and women aged 5 to 21 from LAVENDER (n=154). Symptom scores continued to improve; diarrhea led 21.4% of participants to withdraw [Source](https://pubmed.ncbi.nlm.nih.gov/38917793/)
4. Percy AK et al. Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome. Med. 2025. 2025. Human study (early or uncontrolled). Population: Girls aged 2 to 4 with Rett syndrome (n=15). Weight-based dosing reached the target exposure; diarrhea in 80% and vomiting in 53.3% [Source](https://pubmed.ncbi.nlm.nih.gov/40043705/)
5. Glaze DG et al. Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome. Neurology. 2019. 2019. Controlled human trial. Population: Girls aged 5 to 15 with Rett syndrome (n=82) [Source](https://pubmed.ncbi.nlm.nih.gov/30918097/)
6. Glaze DG et al. A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome. Pediatr Neurol. 2017. 2017. Controlled human trial. Population: Adolescent and adult females with Rett syndrome (n=56) [Source](https://pubmed.ncbi.nlm.nih.gov/28964591/)
7. Berry-Kravis E et al. A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome. Pediatr Neurol. 2020. 2020. Controlled human trial. Population: Adolescent and adult males with fragile X syndrome (n=72) [Source](https://pubmed.ncbi.nlm.nih.gov/32660869/)
8. NCT00805818 — Study of NNZ-2566 in Patients With Traumatic Brain Injury. Human study (early or uncontrolled). Population: Patients with traumatic brain injury (n=261). Completed; no results posted on the registry [Source](https://clinicaltrials.gov/study/NCT00805818)
9. Bickerdike MJ et al. NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke. J Neurol Sci. 2009. 2009. Preclinical: animal or lab study. Population: Rats. Smaller infarct area after induced stroke. Limitations: Lab or animal research: not evidence of a human effect or dose. [Source](https://pubmed.ncbi.nlm.nih.gov/19157421/)

### Registered trials

- [NCT00805818](https://clinicaltrials.gov/study/NCT00805818)

## Safety

Side effects: Diarrhea (82% versus 20% on placebo); Vomiting (29% versus 12%); Fever (9% versus 4%); Seizure (9% versus 6%); Anxiety, decreased appetite and fatigue (each 8% versus 1% to 2%).

Risks: Diarrhea can persist: 49% of those treated had persistent or recurrent diarrhea, and it can lead to dehydration; Weight loss of more than 7% in 12% of patients versus 4% on placebo; Aspiration and aspiration pneumonia after vomiting; Not recommended in severe kidney impairment; lower doses in moderate impairment; Can raise levels of sensitive CYP3A and P-gp substrates; Not studied in people aged 65 and older, and not established in children under 2.

Human safety basis: FDA prescribing information

## Regulatory status

Trofinetide is an FDA-approved product for specific labelled indications. Approval does not extend to the research contexts described on this page, and approved products are prescription medicines.

- FDA status: Approved
- Availability: Prescription-Only

## Frequently asked questions

### What is trofinetide?

Trofinetide is a medicine for Rett syndrome, a rare genetic neurodevelopmental disorder, sold as Daybue oral solution and Daybue Stix powder packets. It is a small synthetic molecule modeled on a three-amino-acid fragment of IGF-1, and it was the first treatment approved for Rett syndrome in the US.

### How does trofinetide work?

Nobody knows for certain. The FDA label says its mechanism in Rett syndrome is unknown. It was designed as a more stable analog of glycine-proline-glutamate, a tripeptide cut from IGF-1 in the brain, and it showed neuroprotective effects in rodent studies.

### Is trofinetide FDA approved?

Yes. FDA approved Daybue oral solution on 10 March 2023 (NDA 217026, Acadia) and Daybue Stix for oral solution on 11 December 2025 (NDA 219884). Both are for Rett syndrome in adults and children aged 2 and older.

### What are the side effects of trofinetide?

Diarrhea is the main one, in 82% of patients versus 20% on placebo in the phase 3 trial, followed by vomiting (29% versus 12%). The label also warns about weight loss and about aspiration after vomiting. This is reference information, not medical advice.

### How well does trofinetide work?

In the 12-week LAVENDER trial, caregiver-rated symptoms improved by 4.9 points versus 1.7 on placebo on a 90-point scale, and clinician ratings were slightly better, at 3.5 versus 3.8 on a 7-point scale. The results were statistically significant, but the difference was modest.

### What compounds are similar to trofinetide?

This library lists IGF-1, mecasermin, davunetide and cerebrolysin alongside trofinetide because they share a growth-factor origin or a neurological research area. They are not equivalents, and only trofinetide is approved for Rett syndrome.

## References

- [DAYBUE (trofinetide) oral solution and DAYBUE STIX for oral solution — FDA prescribing information, DailyMed](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67e6f2d9-21f6-466f-9def-826c6a4b8257)
- [Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study — Nat Med, 2023](https://pubmed.ncbi.nlm.nih.gov/37291210/)
- [Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study — Med, 2024](https://pubmed.ncbi.nlm.nih.gov/38917793/)
- [Results from the phase 2/3 DAFFODIL study of trofinetide in girls aged 2-4 years with Rett syndrome — Med, 2025](https://pubmed.ncbi.nlm.nih.gov/40043705/)
- [Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome — Neurology, 2019](https://pubmed.ncbi.nlm.nih.gov/30918097/)
- [A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Rett Syndrome — Pediatr Neurol, 2017](https://pubmed.ncbi.nlm.nih.gov/28964591/)
- [A Double-Blind, Randomized, Placebo-Controlled Clinical Study of Trofinetide in the Treatment of Fragile X Syndrome — Pediatr Neurol, 2020](https://pubmed.ncbi.nlm.nih.gov/32660869/)
- [NNZ-2566, a novel analog of (1-3) IGF-1, as a potential therapeutic agent for fragile X syndrome — Neuromolecular Med, 2015](https://pubmed.ncbi.nlm.nih.gov/25613838/)
- [NNZ-2566: a Gly-Pro-Glu analogue with neuroprotective efficacy in a rat model of acute focal stroke — J Neurol Sci, 2009](https://pubmed.ncbi.nlm.nih.gov/19157421/)
- [NCT00805818 — NNZ-2566 in traumatic brain injury, phase 2](https://clinicaltrials.gov/study/NCT00805818)

Note: Dose figures are left out of this Markdown version. See the cited sources.