Pegsebrenatide
A long-acting, PEG-coated version of exenatide built to calm brain inflammation; its Parkinson's trial found no benefit
Pegsebrenatide, developed as NLY01 by Neuraly, is exenatide, the GLP-1 drug for type 2 diabetes, with a large polyethylene glycol chain attached so that one injection lasts much longer. Its makers chose it to test an idea from mouse work: that GLP-1 receptor drugs protect neurons by stopping microglia from turning astrocytes toxic. In 255 people with early, untreated Parkinson's disease, weekly injections of 2.5 or 5.0 mg for 36 weeks did no better than placebo, while causing nausea in up to 58%. A trial in multiple sclerosis began in 2026. It is not approved for any use.
Used in human trials: 2.5 mg or 5.0 mg, Once weekly, Injection (Study: early Parkinson's disease, phase 2) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
GLP-1 receptor drugs such as exenatide and semaglutide were made for blood sugar and weight, but the receptor is also found in the brain, and for more than a decade researchers have asked whether these drugs could slow neurodegenerative disease. Pegsebrenatide is one answer to a practical problem in that search: exenatide itself is short-lived and approved as a twice-daily injection. Attaching a 40-kilodalton chain of polyethylene glycol is meant to keep it in circulation long enough to be given once a week.
Its scientific case rests on a 2018 study in Nature Medicine. In mice injected with clumps of α-synuclein, the protein that aggregates in Parkinson's disease, and in mice carrying a human α-synuclein mutation, NLY01 prevented the loss of dopamine-making neurons, improved behaviour and extended life. The authors traced the effect to microglia, the brain's resident immune cells: NLY01 stopped them from releasing the signals that convert astrocytes into a neurotoxic state. Similar protection followed in two Alzheimer's mouse models, a glaucoma model and a model of multiple sclerosis, and it calmed inflammatory cells in a mouse model of ischaemic retinopathy.
Not every animal result agreed. In a mouse model of chemically induced demyelination, NLY01 seemed to protect myelin only because the mice ate less of the toxin-laced food; with the toxin given by tube, the effect vanished, and it did not speed remyelination. A 2021 comparison in MPTP-treated mice found that NLY01 had weak effects next to a dual GLP-1/GIP agonist and, when labelled, did not cross the blood-brain barrier in meaningful amounts, which sits awkwardly with its description as brain-penetrant.
The decisive test was a phase 2 trial at 58 US movement-disorder clinics. Between 2020 and 2023, 255 people with early, untreated Parkinson's disease received 2.5 mg, 5.0 mg or placebo for 36 weeks. Neither dose changed the combined motor and daily-living score (MDS-UPDRS parts II and III) compared with placebo. Gastrointestinal side effects were the price: 61% and 75% on the two doses against 36% on placebo. An exploratory subgroup hinted at motor benefit in younger patients, and later meta-analyses that pooled it with trials of other GLP-1 drugs reported improvement on a quality-of-life scale at 5 mg a week, but neither result was a primary finding.
Pegsebrenatide is not prescribed or sold. Its trials gave it as a weekly injection to volunteers under study protocols; a phase 2 trial in multiple sclerosis at Johns Hopkins was recruiting in October 2026. The doses below are what those trials used.
Mechanism of Action
Pegsebrenatide activates the GLP-1 receptor like exenatide; the PEG chain keeps it in the body long enough for weekly dosing. Its proposed brain effect is indirect, through immune cells.
GLP-1 receptor agonist
It is an engineered exendin-4 that activates GLP-1 receptors, including those on microglia (PMIDs 29892066, 33902708).
PEG for a longer life
A 40 kDa polyethylene glycol chain enlarges the molecule so it is cleared slowly, but the same bulk kept labelled NLY01 out of the mouse brain (PMID 34125470).
Microglia and astrocytes
In mouse models it stopped activated microglia from converting astrocytes into the neurotoxic A1 state, the step its developers proposed protects neurons (PMIDs 29892066, 33147455).
The usual GLP-1 side effects
Like other GLP-1 drugs it caused nausea, in 58% of people on 5.0 mg in the Parkinson's trial (PMID 38101901), and mice given it lost more weight than controls (PMID 37296356).
Published Research
The studies behind pegsebrenatide (NLY01), read from their PubMed abstracts: the phase 2 Parkinson's trial, two meta-analyses that include it, and the mouse studies in Parkinson's, Alzheimer's, multiple sclerosis and eye disease. Exenatide's own trials are on the exenatide entry. Five cards are carded because the abstract names the drug although the title does not.
Phase 2 in early Parkinson's: no benefit
In 255 people with early untreated Parkinson's disease at 58 US clinics, 2.5 mg or 5.0 mg for 36 weeks did not change MDS-UPDRS parts II and III against placebo (differences -0.39 and 0.36 points). Gastrointestinal events affected 61% and 75% against 36% on placebo, nausea 39% and 58% against 19%. A subgroup analysis suggested possible motor benefit in younger people.
Network meta-analysis of GLP-1 drugs
Across five randomised trials (708 patients), GLP-1 drugs did not improve the main motor score overall. In the network analysis, NLY01 at 5 mg a week improved the PDQ-39 quality-of-life scale, while non-motor symptom results diverged by dose; gastrointestinal events were more frequent with the drugs.
Meta-analysis of eight GLP-1 trials
Pooling eight randomised trials of exenatide, lixisenatide, liraglutide and NLY01 (850 patients), the class showed a small motor benefit after treatment and at follow-up, with more weight loss and gastrointestinal events; results were not given for NLY01 separately in the abstract.
Parkinson's models: astrocytes kept from turning toxic
In α-synuclein fibril-injected mice and hA53T transgenic mice, NLY01 protected dopamine neurons, reduced behavioural deficits and prolonged life; it acted by stopping microglia from converting astrocytes to the neurotoxic A1 state.
Two transgenic Alzheimer's models
Repeated injections under the skin blocked β-amyloid-driven microglial activation and reactive astrocyte formation, preserved neurons and improved spatial learning and memory, acting mainly on GLP-1 receptors on microglia.
Multiple sclerosis model (EAE)
Given before onset, NLY01 delayed and softened experimental autoimmune encephalomyelitis, reduced immune cell traffic into the nervous system and later retinal ganglion cell loss; given after onset in a relapsing model, it lowered clinical scores and second attacks.
Demyelination model: no real effect
It appeared to limit cuprizone demyelination only when mice ate the toxin in their chow and lost more weight; with the toxin given by tube there was no protection, and it did not improve remyelination.
Glaucoma model
In mice with raised eye pressure, NLY01 reduced the conversion of astrocytes to the A1 state and the death of retinal ganglion cells, as did deleting the cytokines that drive that conversion.
Ischaemic retinopathy
Injected into the eye in oxygen-induced retinopathy, NLY01 settled in immune cells of the retina, lowered inflammatory cytokines, promoted repair of vessels and suppressed abnormal new vessels.
Weaker than a dual agonist; little brain entry
In MPTP-treated mice at 25 nmol/kg, NLY01 improved motor tests but had weak or no effects on dopamine neurons, α-synuclein, inflammation markers and growth factors compared with the dual agonist DA5-CH, and labelled NLY01 did not cross the blood-brain barrier in meaningful amounts.
Dosing Data
Pegsebrenatide has been given to people only in trials. The amounts below are those of its phase 2 Parkinson's trial; there is no approved dose.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Pegsebrenatide is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
An arithmetic example, not a recommendation: a 5 mg vial mixed with 2 mL of bacteriostatic water holds 2,500 mcg per mL, so every 10 units on a U-100 insulin syringe hold 250 mcg. 2.5 mg, the first amount in the “Study: early Parkinson's disease, phase 2” row (2.5 mg or 5.0 mg) is 100.0 units (1.000 mL). If your vial or water differ, the numbers change: use the reconstitution calculator.
Source: dose: Used in human trials, PMID 38101901; weekly schedule PMID 41995965 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Pegsebrenatide, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Pegsebrenatide stays intact once mixed.
How it is taken
As it was given in human studies: Injection (Once weekly; Study: early Parkinson's disease, phase 2).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: early Parkinson's disease, phase 2: 36 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Pegsebrenatide. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Gastrointestinal disorders in 61% and 75% against 36% on placebo; Nausea in 39% and 58% against 19% on placebo, the most common event overall; Any treatment-emergent adverse event in 84% and 93% against 87% on placebo; No deaths during the study. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Pegsebrenatide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the phase 2 Parkinson's trial (PMID 38101901), 2.5 mg and 5.0 mg against placebo”).
Interactions
Unknown: a PubMed search for human interaction studies of Pegsebrenatide (reviewed 2026-10-30) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Pegsebrenatide products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Not approved: Drugs@FDA (openFDA) holds no record and the EMA medicines list no entry (searched October 30, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the phase 2 Parkinson's trial (PMID 38101901), 2.5 mg and 5.0 mg against placebo.
Contraindications & Cautions
No label exists. These cautions follow from its trial and its drug class.
Legal Status
Pegsebrenatide is an investigational drug with no marketing approval anywhere.
Frequently Asked Questions
?What is NLY01?
NLY01, named pegsebrenatide, is exenatide with a large polyethylene glycol chain attached so it lasts about a week. It was developed to test GLP-1 drugs against brain inflammation in Parkinson's disease.
?Did it work in Parkinson's disease?
No. In a 36-week trial of 255 people with early Parkinson's, neither 2.5 mg nor 5.0 mg improved motor or non-motor symptoms compared with placebo. A possible benefit in younger patients was exploratory.
?Is it the same as exenatide?
It is built from exendin-4, the peptide in exenatide, but with a 40 kDa PEG chain, so it behaves differently in the body. Exenatide's own Parkinson's trials are on the exenatide entry.
?Does it get into the brain?
Its developers called it brain-penetrant, but a 2021 mouse study found that labelled NLY01 did not cross the blood-brain barrier in meaningful amounts.
?Is it still being studied?
Yes. A phase 2 trial in multiple sclerosis at Johns Hopkins was recruiting in October 2026.
?Can it be used for weight loss?
No study of weight loss with it has been published. It is not approved for any use and is not sold.
References
- [clinical-trial] McGarry A, et al. "Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial." Lancet Neurol, 2024;23(1):37-45. PMID: 38101901.
- [review] Ali M, et al. "Efficacy of GLP-1 receptor agonists in Parkinson's disease: a systematic review and exploratory network meta-analysis of randomized controlled trials." Neurol Sci, 2026;47(5). PMID: 41995965.
- [review] Chen Y, et al. "GLP-1 receptor agonists in Parkinson's disease: a meta-analysis revealing motor benefit and highlighting mood improvement." Front Neurol, 2026;17:1858507. PMID: 42490867.
- [pubmed] Yun SP, et al. "Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease." Nat Med, 2018;24(7):931-938. PMID: 29892066.
- [pubmed] Park JS, et al. "Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer's disease." Acta Neuropathol Commun, 2021;9(1):78. PMID: 33902708.
- [pubmed] Zhou L, et al. "Myeloid cell modulation by a GLP-1 receptor agonist regulates retinal angiogenesis in ischemic retinopathy." JCI Insight, 2021;6(23). PMID: 34673570.
- [pubmed] Gharagozloo M, et al. "Therapeutic Potential of a Novel Glucagon-like Peptide-1 Receptor Agonist, NLY01, in Experimental Autoimmune Encephalomyelitis." Neurotherapeutics, 2021;18(3):1834-1848. PMID: 34260042.
- [pubmed] Gharagozloo M, et al. "The Effects of NLY01, a Novel Glucagon-Like Peptide-1 Receptor Agonist, on Cuprizone-Induced Demyelination and Remyelination: Challenges and Future Perspectives." Neurotherapeutics, 2023;20(4):1229-1240. PMID: 37296356.
- [pubmed] Sterling JK, et al. "GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension." Cell Rep, 2020;33(5):108271. PMID: 33147455.
- [pubmed] Lv M, et al. "The GLP-1/GIP dual-receptor agonist DA5-CH inhibits the NF-κB inflammatory pathway in the MPTP mouse model of Parkinson's disease more effectively than the GLP-1 single-receptor agonist NLY01." Brain Behav, 2021;11(8):e2231. PMID: 34125470.
- [registry] ClinicalTrials.gov API v2, read October 30, 2026: NCT03672604 (phase 1 in healthy subjects, Neuraly, 96 enrolled, completed July 2019); NCT04154072 (phase 2 in early Parkinson's disease, 255 enrolled, arms 'NLY01 2.5 mg injection' and 'NLY01 5.0 mg injection', intervention described as 'exenatide and polyethylene glycol (PEG)', completed February 2023); NCT04159766 (phase 2 in type 2 diabetes, 20 enrolled, completed December 2020); NCT07497399 (TAG-MS, phase 2 in multiple sclerosis, Johns Hopkins University, 120 planned, '5 mg subcutaneous weekly for the first 4 weeks, then 10 mg subcutaneous weekly', recruiting). https://clinicaltrials.gov/study/NCT07497399
- [other] ChEMBL CHEMBL4650495 (pegsebrenatide; synonyms NLY01, NLY-01): biotherapeutic, peptide component HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSFAPPPSC; no full molecular formula given. Read October 30, 2026. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL4650495/
- [other] US FDA, Drugs@FDA (openFDA drugsfda endpoint), searched October 30, 2026: no application for pegsebrenatide or NLY01.
Sources & Citations
Every study on this page was read from its PubMed record on October 30, 2026. Trial designs and status come from ClinicalTrials.gov, regulatory status from Drugs@FDA and the EMA medicines list, and the peptide chain from ChEMBL, all read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.