Evidence map›Paper›PMID 42608956›Full record

ArticleBrain and behavior2026

The Neuroprotective Potentials of Dual GIP/GLP1-RA (Tirzepatide): From Preclinical Experiments to Clinical Trials: A Scoping Review.

Yousef Hawas, Mohamed Abouzid, Ahmed Farid Gadelmawla, Dalia Kamal Ewis, Abdallah Khatatbeh, Yasmin Negida, Ahmed Negida

Abstract readScoping Review
In one paragraph

Article in Brain and behavior, 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

7 authors.

Yousef HawasFaculty of Medicine, Tanta University, Tanta, Egypt.ORCID https://orcid.org/0000-0003-0361-4609
Mohamed AbouzidDepartment of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland.ORCID https://orcid.org/0000-0002-8917-671X
Ahmed Farid GadelmawlaMedical Research Group of Egypt, Arlington, Massachusetts, USA.ORCID https://orcid.org/0000-0002-5802-2291
Dalia Kamal EwisMedical Research Group of Egypt, Arlington, Massachusetts, USA.ORCID https://orcid.org/0009-0008-4300-8113
Abdallah KhatatbehAl-Hussein Medical Center, Jordanian Royal Medical Services, Amman, Jordan.ORCID https://orcid.org/0000-0001-8299-6945
Yasmin NegidaFaculty of Medicine, Zagazig University, Zagazig, Egypt.ORCID https://orcid.org/0009-0001-4018-8146
Ahmed NegidaMedical Research Group of Egypt, Arlington, Massachusetts, USA.ORCID https://orcid.org/0000-0001-5363-6369

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTirzepatide (TZP), the first approved dual glucagon-like peptide 1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) agonist, has shown neuroprotective effects in preclinical models and early observational studies. This review maps and appraises current preclinical and clinical evidence on TZP's potential neuroprotective effects in neurodegenerative diseases (Alzheimer's and Parkinson's disease), neuroinflammation, cerebrovascular outcomes, neurovestibular disorders, brain tumor response, and idiopathic intracranial hypertension.

methodsPubMed, Scopus, Web of Science, Embase, and Elton B. Stephens Company (EBSCO) were searched through September 30, 2025. Eligible sources included original preclinical or clinical studies reporting neurological or neuroprotective effects of TZP. Quality was assessed using SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADE) for in vivo studies, toxicological data reliability assessment tool (ToxRTool) for in vitro, Newcastle-Ottawa scale (NOS) for cohorts, and Joanna Briggs Institute (JBI) for case reports.

resultsTwenty-two studies met inclusion criteria as follows: 11 preclinical investigations, 3 retrospective cohorts, and 8 case reports. Preclinical studies demonstrated mitochondrial stabilization (adenosine triphosphate [ATP] restoration; PINK1/Parkin), anti-oxidative and anti-inflammatory signaling, synaptic support (PSD-95/synaptophysin), and blood-brain barrier reinforcement (claudin-1), alongside behavioral improvements. Retrospective cohorts reported reduced cerebrovascular and neurodegenerative disease incidence, papilledema, and headaches, though one cohort identified higher risk of central vertigo and vestibular neuronitis. Case reports documented compression neuropathies, autoimmune encephalitis, hypoglycemia-related seizures, psychiatric reactions, and rhabdomyolysis, most resolving with dose adjustment or discontinuation. Risk-of-bias appraisal revealed frequent "unclear" ratings in animal studies, "reliable with restrictions" in vitro, and high NOS scores for cohorts.

conclusionsTZP exhibits biologically plausible neuroprotective mechanisms preclinically. Prospective trials with standardized neurological endpoints, active-comparator designs, and structured safety monitoring are warranted.

Indexed as

Neurodegenerative DiseasesNeuroprotective AgentsTirzepatideAnimalsHumansNeuroprotective AgentsTirzepatideAlzheimercerebrovasculardementiaglucose‐dependent insulinotropic polypeptide (GIP)/glucagon‐like peptide 1 (GLP‐1)neuroprotectionParkinsontirzepatide

Identifiers

PMID42608956
PMCPMC13482023

What Socratic holds

Textmetadata
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 Socratic graph.