Evidence map›Paper›PMID 40172827›Full record

ReviewNeurology and therapy2025

Are Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Central Nervous System (CNS) Penetrant: A Narrative Review.

Juliana West, Maggie Li, Sabrina Wong, Gia Han Le, Kayla M Teopiz, Kyle Valentino, Christine E Dri, Roger S McIntyre

Erratum issuedAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neurology and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Juliana West *Brain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
Maggie Li *Brain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
Sabrina WongBrain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
Gia Han LeBrain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
Kayla M TeopizBrain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
Kyle ValentinoBrain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
Christine E DriBrain and Cognition Discovery Foundation, 77 Bloor Street West, Suite 617, Toronto, ON, M5S 1M2, Canada.
Roger S McIntyreDepartment of Psychiatry, University of Toronto, Toronto, Canada. roger.mcintyre@bcdf.org.ORCID http://orcid.org/0000-0003-4733-2523

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionGlucagon-like peptide-1 (GLP-1) is an incretin hormone that modulates glucose metabolism and insulin secretion. Recent translational and clinical research has evaluated the effects of GLP-1 receptor agonists (GLP-1 RAs), a class of drugs that mimic the action of native GLP-1 in the central nervous system (CNS). In addition to the efficacy of GLP-1 for the treatment of diabetes mellitus and obesity, preliminary evidence indicates GLP-1s have neuroprotective, therapeutic, and disease modification effects for select neurodegenerative disorders (e.g. Parkinson's disease, Alzheimer's disease). Among the available GLP-1 RAs, relatively few have been shown to be CNS penetrant. This article synthesizes extant literature reporting on CNS penetrants of GLP-1 RAs as proxied by brain imaging studies. Where available, studies that reported on the bioavailability of GLP-1 RAs in the CNS were identified.

methodsA comprehensive search of PubMed, Ovid, and Web of Science from database inception to July 2024 was conducted. Inclusion criteria were English language publications with no date restrictions, preclinical and clinical studies with participants aged 18-80 and studies which focused on GLP-1 RAs including: "Semaglutide" or "Ozempic" or "Rybelsus" or "Wegovy" or "Dulaglutide" or "Trulicity" or "Exenatide" or "Byetta" or "Bydureon" or "Liraglutide" or "Lixisenatide" or "Tirzepatide" or "Mounjaro" or "Zepbound" or "Bydureon BCise" or "Adlyxin" or "Victoza" or "Saxenda".

resultsWe identified 14 studies that were included in this synthesis. Preclinical studies suggest that select GLP-1 RAs cross the blood-brain barrier (BBB) (i.e. liraglutide, semaglutide, and exenatide). Replicated evidence suggests that CNS penetration of GLP-1 RAs can be proxied by reported effects of GLP-1 RAs on brain connectivity in human participants.

conclusionPreclinical studies indicate that select GLP-1 RAs are CNS penetrant; whether GLP-1 RAs reproducibly engage neural targets hypothesized to subserve dimensions of psychopathology (e.g., general cognitive functions) remains incompletely characterized.

Indexed as

Blood–brain barrierDulaglutideExenatideGLP-1LiraglutideLixisenatideSemaglutideTirzepatide

Identifiers

PMID40172827
PMCPMC12255637

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.