FDA-approved
Brain & sleep
Trofinetide
Also called GPE analog (glycine-proline-glutamate)
Trofinetide (DAYBUE) is an FDA-approved drug for Rett syndrome. Learn how it works, what it is prescribed for, its side effects, and the evidence.
- Reviewed by
- William Maish, MD MBA MPH, Clinical Product Lead
- Published
- October 5, 2026
- Last updated
- October 5, 2026
Key takeaway
Trofinetide (sold as DAYBUE and DAYBUE Stix) is a synthetic analog of a small fragment of insulin-like growth factor 1, and the first drug the FDA approved for Rett syndrome, a rare genetic disorder, in 2023. In the 12-week LAVENDER phase 3 trial1 of 187 females, scores on the caregiver-rated Rett Syndrome Behaviour Questionnaire fell 4.9 points on trofinetide versus 1.7 on placebo (P = 0.0175). Clinician global impression also improved significantly on trofinetide versus placebo.
At a glance
| What it is | A synthetic analog of the IGF-1-derived tripeptide glycine-proline-glutamate (GPE) |
| Approved for | Rett syndrome in adults and children 2 and older |
| Key fact | In the LAVENDER trial it significantly improved caregiver and clinician measures of Rett syndrome versus placebo |
| Brands | DAYBUE and DAYBUE STIX |
| Evidence strength | FDA approved |
What is trofinetide?
Trofinetide, sold under the brands DAYBUE and DAYBUE Stix, is a synthetic analog of glycine-proline-glutamate (GPE), a three-amino-acid fragment naturally cleaved from insulin-like growth factor 1 (IGF-1) in the brain. It is the first medication approved specifically for Rett syndrome, a rare genetic disorder, almost always in girls, that causes loss of acquired skills, movement problems, and impaired communication. It was approved in the United States in 2023.
How does trofinetide work?
The precise way trofinetide helps in Rett syndrome is not fully established, which the labeling acknowledges. Based on preclinical work, it is thought to act on several of the processes disturbed in the condition:
- Reducing neuroinflammation by modulating the brain's immune cells (microglia and astrocytes)
- Supporting the formation and maturation of synapses and dendrites
- Normalizing signaling related to IGF-1 in the central nervous system
The aim is to improve the function of brain circuits affected by the loss of the MECP2 gene that causes Rett syndrome.
Because Rett syndrome had no approved drug treatment before it, trofinetide's benefit is measured on scales of behavior and overall clinical impression rather than a single biomarker. In the phase 3 LAVENDER trial, trofinetide significantly improved both the caregiver-rated Rett Syndrome Behaviour Questionnaire and a clinician's global impression1 compared with placebo. The trial randomized 187 females for 12 weeks (P = 0.0175 for the questionnaire difference):
| Arm | Females randomized | Questionnaire score change |
| Trofinetide | 93 | Fell 4.9 points1 |
| Placebo | 94 | Fell 1.7 points |
The most common effects of trofinetide are gastrointestinal.
Is it FDA-approved?
Yes. Trofinetide (DAYBUE) was approved2 by the FDA in 2023 for the treatment of Rett syndrome in adults and children 2 years and older. It was the first approved treatment for the condition. DAYBUE Stix, a powder that is mixed into a solution, appears in the current prescribing information3, revised in December 2025.
What is trofinetide prescribed for?
Trofinetide is prescribed for Rett syndrome in people 2 years and older. Because diarrhea is common, medicines that can worsen diarrhea or dehydration are used carefully alongside it.
What are the side effects?
According to the prescribing information, common side effects include:
- Diarrhea, which most patients experience
- Vomiting
- Fever
- Decreased appetite and fatigue
- Anxiety
- Seizure
- Cold symptoms
More serious considerations include:
- Diarrhea and dehydration, which may require managing fluids and adjusting other medicines
- Severe vomiting, which can lead to aspiration3 of stomach contents
- Significant weight loss, so weight is monitored
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Sources: FDA prescribing information for DAYBUE; the LAVENDER trial (Neul et al., Nature Medicine, 2023, DOI: 10.1038/s41591-023-02398-11), indexed on PubMed. This document is educational and does not constitute medical advice.