Evidence map›Paper›PMID 39904872›Full record

ArticleNeurocritical care2025

The Dipeptidyl Peptidase-4 Inhibitor Saxagliptin as a Candidate Treatment for Disorders of Consciousness: A Deep Learning and Retrospective Clinical Analysis.

Daniel Toker, Jeffrey N Chiang, Paul M Vespa, Caroline Schnakers, Martin M Monti

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurocritical care, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
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

5 authors.

Daniel TokerDepartment of Neurology, University of California, Los Angeles, Los Angeles, CA, USA. danieltoker@g.ucla.edu.
Jeffrey N ChiangDepartment of Computational Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Paul M VespaDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, USA.
Caroline SchnakersResearch Institute, Casa Colina Hospital and Centers for Healthcare, Pomona, CA, USA.
Martin M MontiDepartment of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite advancements in the neuroscience of consciousness, no new medications for disorders of consciousness (DOC) have been discovered in more than a decade. Repurposing existing US Food and Drug Administration (FDA)-approved drugs for DOC is crucial for improving clinical management and patient outcomes.

methodsTo identify potential new treatments among existing FDA-approved drugs, we used a deep learning-based drug screening model to predict the efficacy of drugs as awakening agents based on their three-dimensional molecular structure. A retrospective cohort study from March 2012 to October 2024 tested the model's predictions, focusing on changes in Glasgow Coma Scale (GCS) scores in 4047 patients in a coma from traumatic, vascular, or anoxic brain injury.

resultsOur deep learning drug screens identified saxagliptin, a dipeptidyl peptidase-4 inhibitor, as a promising awakening drug for both acute and prolonged DOC. The retrospective clinical analysis showed that saxagliptin was associated with the highest recovery rate from acute coma among diabetes medications. After matching patients by age, sex, initial GCS score, coma etiology, and glycemic status, brain-injured patients with diabetes on incretin-based therapies, including dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 analogues, recovered from coma at significantly higher rates compared to both brain-injured patients with diabetes on non-incretin-based diabetes medications (95% confidence interval of 1.8-14.1% higher recovery rate, P = 0.0331) and brain-injured patients without diabetes (95% confidence interval of 2-21% higher recovery rate, P = 0.0272). Post matching, brain-injured patients with diabetes on incretin-based therapies also recovered at a significantly higher rate than patients treated with amantadine (95% confidence interval for the difference 2.4-25.1.0%, P = 0.0364). A review of preclinical studies identified several pathways through which saxagliptin and other incretin-based medications may aid awakening from both acute and chronic DOC: restoring monoaminergic and GABAergic neurotransmission, reducing brain inflammation and oxidative damage, clearing hyperphosphorylated tau and amyloid-β, normalizing thalamocortical glucose metabolism, increasing neural plasticity, and mitigating excitotoxic brain damage.

conclusionsOur findings suggest incretin-based medications in general, and saxagliptin in particular, as potential novel therapeutic agents for DOC. Further prospective clinical trials are needed to confirm their efficacy and safety in DOC.

Indexed as

AdamantaneConsciousness DisordersDeep LearningDipeptidesDipeptidyl-Peptidase IV InhibitorsAdultAgedDrug RepositioningFemaleGlasgow Coma ScaleHumansMaleMiddle AgedRetrospective StudiesAdamantaneDipeptidesDipeptidyl-Peptidase IV InhibitorssaxagliptinArtificial intelligenceComaDisorders of consciousnessIncretinMinimally conscious statePersistent vegetative state

Identifiers

PMID39904872
PMCPMC12321933

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.