Evidence mapPaperPMID 41607204Full record

SynthesisCNS spectrums2026

Investigating the functional connectivity between central glucagon-like peptide-1 (GLP-1) and glutamatergic signaling: a systematic review.

Sabrina Wong, Gia Han Le, Kayla Teopiz, Roger S McIntyre

Abstract readSystematic Review
In one paragraph

Synthesis in CNS spectrums, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Sabrina WongDepartment of Pharmacology & Toxicology, https://ror.org/03dbr7087University of Toronto, Canada.
Gia Han LeMood Disorders Psychopharmacology Unit, https://ror.org/042xt5161University Health Network, Canada.
Kayla TeopizMood Disorders Psychopharmacology Unit, https://ror.org/042xt5161University Health Network, Canada.
Roger S McIntyreDepartment of Pharmacology & Toxicology, https://ror.org/03dbr7087University of Toronto, Canada.ORCID 0000-0003-4733-2523

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glutamatergic neurons represent 40% of neurons in the human central nervous system. Glutamate accounts for approximately 90% of all excitatory neurotransmitters. Previous research reports the presence of glucagon-like peptide-1 (GLP-1) receptors on neurons that produce glutamate. Herein, we aim to evaluate whether GLP-1 receptor agonists' (GLP-1 RAs) modulate glutamatergic signaling and whether GLP-1 RAs' anti-obesity effects are mediated through the glutamatergic system. We conducted a systematic review of extant literature published on PubMed, Ovid and Scopus databases from inception to March, 2025. Identified studies were screened independently by two reviewers (S.W. and G.H.L.) using the Covidence platform. We sought to include in vitro, in vivo, and human clinical studies. A total of 31 studies were identified as meeting eligibility for an inclusion in this review. No human studies were identified. Across the included preclinical and pharmacologic studies, GLP-1 RAs were associated with increased glutamate release, NMDA/AMPA receptor activation and increased release of neurotrophic factors associated with neurogenesis, neurodifferentiation, and synaptic plasticity. In addition, GLP-1 RA-induced suppression of food intake was reported to be dependent on AMPA, but not NMDA, receptor signaling. The effect of GLP-1 RAs on feeding behavior is mediated via central glutamatergic signaling. A comprehensive mechanistic framework mediating GLP-1 RA activity implicates crosstalk between GLP-1 and ionotropic glutamate receptors. The aforementioned trends instantiate a need to evaluate the therapeutic efficacy of GLP-1 RAs for disparate neuropsychiatric disorders. Conducting target engagement studies of GLP-1 RAs with the glutamatergic system in humans is a future research vista.

Indexed as

Glucagon-Like Peptide 1Glutamic AcidNeuronsAnimalsGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHumansSignal TransductionGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlutamic AcidAMPAGLP-1Glucagon-like peptide-1glutamatergic modulatorsglutamatergic systemNMDA

Identifiers

PMID41607204
PMCPMC13076071

What Socratic holds

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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 Socratic graph.