Evidence map›Paper›PMID 42165019›Full record

ArticleFrontiers in endocrinology2026

The novel GLP-1/GIP dual receptor agonist DA5-CH is superior to tirzepatide and exendin-4 in the 6-OHDA Parkinson rat model.

Zhang Lingyu, Feng Peng, Zhong Wanting, Jin Qianqian, Zijuan Zhang, Bo Bai, Guofang Xue, Christian Hölscher

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Zhang LingyuExperimental Animal Center of Shanxi Medical University, Shanxi Key Laboratory of Human Disease and Animal Models, Taiyuan, Shanxi, China.
Feng PengSecond Hospital, Neurology Department, Shanxi Medical University, Taiyuan, Shanxi, China.
Zhong WantingSchool of Medical Science, Shanxi Medical University, Taiyuan, Shanxi, China.
Jin QianqianDepartment of Forensic Pathology, Shanxi Medical University, Taiyuan, Shanxi, China.
Zijuan ZhangSchool of Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Bo BaiSecond Hospital, Neurology Department, Shanxi Medical University, Taiyuan, Shanxi, China.
Guofang XueSecond Hospital, Neurology Department, Shanxi Medical University, Taiyuan, Shanxi, China.
Christian HölscherSecond Hospital, Neurology Department, Shanxi Medical University, Taiyuan, Shanxi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disorder for which there is no cure. Diabetes is one of the risk factors for developing PD. Tirzepatide is a novel long-acting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist that is on the market as a treatment for diabetes. Importantly, two phase II trials in PD patients showed good effects with the GLP-1 receptor agonists Exendin-4 and Lixisenatide. Methods: We have developed a dual GLP-1/GIP receptor agonist (DA5-CH) that can cross the blood-brain barrier (BBB) at a higher rate than Tirzepatide. Here, we tested Exendin-4, Tirzepatide and DA5-CH in the 6-OHDA-lesion rat model of PD. The drug treatment was daily (10 nmol/kg, ip.) for 30 days. Results: DA5-CH was more effective than Tirzepatide or Exendin-4. In the substantia nigra, dopaminergic neurons were protected, with DA5-CH being most effective. Dopamine levels in the striatum were normalized by DA5-CH, while Exendin-4 was less effective, and Tirzepatide was ineffective. The inflammation response in the lesioned striatum was reduced by the drugs as shown in reduced IL-6 and TNF-α levels, with DA5-CH being more effective than Exendin-4, and Tirzepatide showing minimal effects. Furthermore, the α-synuclein levels in the substantia nigra were reduced by DA5-CH, superior to Exendin-4 and Tirzepatide. Discussion: Therefore, DA5-CH was more effective and may be a better therapeutic drug for neurodegenerative disorders such as PD compared to Tirzepatide or Exendin-4.

Indexed as

ExenatideGlucagon-Like Peptide-1 Receptor AgonistsReceptors, Gastrointestinal HormoneAnimalsDisease Models, AnimalMaleOxidopamineRatsRats, Sprague-DawleyTirzepatideExenatidegastric inhibitory polypeptide receptorGlucagon-Like Peptide-1 Receptor AgonistsOxidopamineReceptors, Gastrointestinal HormoneTirzepatidecytokinesGLP-1growth factorinflammationinsulinmitochondria

Identifiers

PMID42165019
PMCPMC13183531

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Registered trials

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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.