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Abstract Details

Neuroprotective Effects of Tirzepatide: A Scoping Review of Preclinical and Clinical Evidence
General Neurology
P11 - Poster Session 11 (11:45 AM-12:45 PM)
7-002
To systemically review and summarize existing preclinical and clinical evidence on the neurological and neuroprotective effects of Tirzepatide.

Tirzepatide (TZP), a dual GLP-1/GIP agonist, has emerged as a promising drug for managing Type 2 diabetes mellitus. Recent studies have demonstrated the neuroprotective effect of TZP through modulation of insulin signaling, anti-inflammatory effects, and neurotrophic support. 

PubMed, Scopus, Web of Science, Embase, and EBSCO were searched to July 30th, 2025. Eligible sources were original preclinical or clinical studies reporting neurological or neuroprotective effects of TZP. Data were extracted by two independent authors in an Excel sheet and synthesized narratively. Quality assessment tools were used as follows: SYRCLE for in vivo studies, ToxRTool for in vitro, NOS for cohorts, and JBI for case reports.
22 studies met the inclusion criteria;11 preclinical investigations, three retrospective cohorts, and 8 case reports. Preclinical work indicated mitochondrial stabilization (ATP restoration; PINK1/Parkin), anti-oxidative and anti-inflammatory signaling, synaptic support (PSD-95/synaptophysin), and reinforcement of the blood–brain barrier (claudin-1), with behavioral gains in selected models. Retrospective cohorts showed a positive association with a reduction of cerebrovascular and neurodegenerative disease, Papilledema, and Headaches. One Cohort showed a higher risk of central vertigo and vestibular neuronitis. Case reports described uncommon presentations such as compression neuropathies with rapid weight loss, autoimmune encephalitis, hypoglycemia-related seizures, psychiatric reactions, and rhabdomyolysis that generally improved after dose adjustment, supportive care, or cessation. The appraisal revealed frequent “unclear” risk in animal studies, “reliable with restrictions” in vitro, high NOS scores for cohorts, and adequate JBI reporting.
Tirzepatide (TZP) exhibits biologically plausible neuroprotective actions in cells and animals; however, clinical evidence is preliminary and indirect. Prospective trials with standardized neurological endpoints, active-comparator designs, and structured safety monitoring are needed.
Authors/Disclosures
YASMIN NEGEDA, MD
PRESENTER 		Dr. NEGEDA has nothing to disclose.
Yousef A. Hawas Mr. Hawas has a non-compensated relationship as a Faculty with 好色先生 Institution (AANI); NeuroBytes: Medical Students Series that is relevant to AAN interests or activities.
Mohamed Abouzid Mohamed Abouzid has nothing to disclose.
Ahmed Farid, MD Dr. Farid has nothing to disclose.
Dalia Kamal Ewis, MD Miss Ewis has nothing to disclose.