Evidence review: Open Peptide Project (verified against primary PubMed, ClinicalTrials.gov & FDA records) · Last checked 2026-10-27. ← Back to Evidence Library

Trofinetide (Daybue, NNZ-2566): what the evidence says

Name: Trofinetide (Daybue, NNZ-2566)
Published: 2026-10-27

At a glance

What it is: a synthetic analog of glycine-proline-glutamate (GPE), a fragment of IGF-1. Approved as an oral solution (Daybue, Mar 2023) for Rett syndrome in patients 2 years and older; a powder form (Daybue Stix) was approved Dec 2025. ^{R1, R2, R3}

What the evidence says: Human in the LAVENDER phase 3 trial (187 girls and women with Rett syndrome), trofinetide modestly improved caregiver-rated symptoms and clinician global ratings vs placebo. ^R4 There are no trials of trofinetide for memory, focus or any non-Rett use.

Biggest risks: diarrhea is very common (about 4 in 5 patients in LAVENDER); label warnings also cover weight loss and vomiting with risk of aspiration. ^{R4, R3}

Rating


Human Human evidence	Strong: LAVENDER RCT (n = 187) plus open-label extensions ^{R4, R5}
Animal Animal / lab evidence	Not reviewed
Regulatory	FDA-approved ^R1 · not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page ^{R6, R7, R8} · not named by WADA ^R9
Established human dose	Yes, label dose (see Study details)

Evidence verdict: Rett syndrome: Strong (phase 3 RCT) · Use as a nootropic or for other conditions: No human data

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: one pivotal RCT with modest effect sizes on caregiver and clinician scales; extensions were open-label.

What is it?

Related pages: nnz-2591, igf-1-mecasermin.

Does it work?

Human LAVENDER (12 weeks): RSBQ score change −4.9 vs −1.7 with placebo; clinician global improvement 3.5 vs 3.8 (lower is better). ^R4
🟨 LILAC and LILAC-2: open-label extensions (154 and 77 patients) suggested continued improvement over longer use. ^{R5, R10}
🟨 DAFFODIL: open-label study in 15 girls aged 2 to 4. ^R11
⚪ Nootropic or other uses: no human data.

Is it safe?

Human Diarrhea 80.6% vs 19.1% with placebo; vomiting also more common. ^R4
🟨 In LILAC, diarrhea 74.7% and vomiting 28.6%. ^R5
Label warnings: diarrhea, weight loss, vomiting and aspiration. ^R3

Gray-market vials: extra risks

A gray-market vial has no quality control and no guarantee of identity, strength or sterility. We test retail vials blind under the Open Peptide Standard; see /tests/. A passing test covers one batch on one date and does not mean the compound is safe.

Is it legal?

US: FDA-approved, prescription (Daybue, Daybue Stix). ^{R1, R2}
Compounding: not on FDA's 503A or 503B bulk-substance category lists and not on FDA's compounding safety-risk page. ^{R6, R7, R8}
Sport: not named on WADA's 2026 Prohibited List. ^R9

Study details

These are amounts researchers used, not recommendations.

Study	People / model	Route	Amount used	Follow-up	Reported	Citation
LAVENDER 2023	187 females with Rett syndrome	Oral	Weight-based, per label	12 weeks	RSBQ −4.9 vs −1.7; CGI-I 3.5 vs 3.8	PMID 37291210
LILAC 2024	154 from LAVENDER	Oral	Weight-based, per label	40 weeks, open-label	Continued improvement; diarrhea 74.7%	PMID 38917793
LILAC-2 2024	77 from LILAC	Oral	Weight-based, per label	32 months, open-label	Continued improvement	PMID 39025065
DAFFODIL 2025	15 girls, 2 to 4 years	Oral	Weight-based, per label	About 2 years, open-label	Diarrhea 80%, vomiting 53.3%; symptoms improved	PMID 40043705

Full reference list (PubMed, CT.gov, FDA and WADA checked Oct 27, 2026)

^R1 Drugs@FDA, Daybue (trofinetide), application NDA217026 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA217026
^R2 Drugs@FDA, Daybue Stix (trofinetide), application NDA219884 (openFDA drugsfda record checked Oct 27, 2026). https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=NDA219884
^R3 Daybue prescribing information, label published Sep 4, 2026 (DailyMed, checked Oct 27, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=67e6f2d9-21f6-466f-9def-826c6a4b8257
^R4 Neul JL, et al. Nat Med. 2023. PMID 37291210
^R5 Percy AK, et al. Med. 2024. PMID 38917793
^R6 FDA, 503A bulk drug substances categories list (updated May 14, 2026). https://www.fda.gov/media/94155/download
^R7 FDA, 503B bulk drug substances categories list (updated Mar 21, 2025). https://www.fda.gov/media/94164/download
^R8 FDA, Certain bulk drug substances for use in compounding that may present significant safety risks (content current Apr 22, 2026). https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
^R9 WADA. The 2026 Prohibited List, full list checked; compound not named. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
^R10 Percy AK, et al. Med. 2024. PMID 39025065
^R11 Percy AK, et al. Med. 2025. PMID 40043705

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use Trofinetide (Daybue, NNZ-2566). This is a prescription medicine. Use it only under the care of a licensed clinician; do not buy it from research-chemical or gray-market sellers. Report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).