Evidence map›Paper›PMID 42410323›Full record

ArticleDiabetes, obesity & metabolism2026

A Sequential Dual GLP-1R/GIPR Agonist-To-Antagonist Molecule Achieves Superior Weight Loss in Obese Mice.

Yunxiao Zhang, Bo Zhu, Binhui Peng, Peng Wu, Guyu Zhong, Yongchen Wang, Zhaofeng Wang, Xinyu Feng, Dongfang Tang, Dezheng Peng and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, obesity & metabolism, 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. Article
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

11 authors.

Yunxiao ZhangSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.ORCID 0009-0004-0491-6769
Bo ZhuSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Binhui PengSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Peng WuSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Guyu ZhongSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Yongchen WangSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Zhaofeng WangSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Xinyu FengSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Dongfang TangDepartment of Chemical and Biological Engineering, Hunan University of Science and Engineering, Yongzhou, Hunan, China.
Dezheng PengSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.
Yu LiuSchool of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, Hunan, China.

Funding

Hunan Provincial College Students Innovation and Entrepreneurship Program S202510543075National College Students Innovation and Entrepreneurship Program S202410543042National Natural Science Foundation of China 32371327Natural Science Foundation of Hunan Province 2022JJ40159Postgraduate Scientific Research Innovation Proiect of Hunan Province YCX2024A23Research Foundation of the Education Department of Hunan Province 22A0572
6 · The paper itself

Abstract

backgroundThe GLP-1 receptor (GLP-1R) and GIP receptor (GIPR) are key targets for diabetes and obesity therapies. Pharmacological agents including GLP-1R agonists (e.g., Semaglutide), dual GLP-1R/GIPR agonists (e.g., Tirzepatide) and a GLP-1R agonist/GIPR antagonist (AMG133) have demonstrated considerable promise in anti-diabetic and weight management applications. However, a systematic comparison of the specific contributions of GIPR activation versus GIPR inhibition to weight loss within the context of GLP-1/GIP dual-targeting therapies remains unexplored. RESEARCH DESIGN AND

methodsTo address this, we designed three IgG4 Fc-fusion proteins: a GLP-1R agonist/GIPR agonist, (i) GLP-1(A8G)/GIP(A2G)-Fc; a GLP-1R agonist/GIPR inhibitor, (ii) GLP-1(A8G)/GIP(3-30)-Fc; and a sequential molecule that hypothesised to transition from dual GLP-1R/GIPR agonism to GLP-1R agonism/GIPR inhibition, (iii) GLP-1(A8G)/GIP(1-30)-Fc. Mono-agonist GLP-1(A8G)-Fc and dual-agonist GLP-1(A8G)/GIP(A2G)-Fc were used as controls to investigate the weight loss effects of GIPR activation and inhibition in DIO mice.

resultsOur findings revealed that the sequential molecule GLP-1(A8G)/GIP(1-30)-Fc produced the greatest body weight reduction (21.59%), significantly outperforming GLP-1(A8G)/GIP(3-30)-Fc (14.5%; p < 0.001). Furthermore, both GIPR activation and inhibition, when combined with GLP-1R agonism, markedly improved serum and hepatic lipid metabolism, as evidenced by reduced triglycerides and total cholesterol.

conclusionTogether, these findings validate a peptide-based inhibitory strategy for synergistic weight loss and provide insights into the differential metabolic roles of GIPR activation versus inhibition, guiding the development of novel anti-obesity therapeutics.

Indexed as

Anti-Obesity AgentsGlucagon-Like Peptide-1 Receptor AgonistsObesityReceptors, Gastrointestinal HormoneWeight LossAnimalsGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorHypoglycemic AgentsMaleMiceMice, Inbred C57BLMice, ObeseRecombinant Fusion ProteinsSemaglutideTirzepatideAnti-Obesity Agentsgastric inhibitory polypeptide receptorGlp1r protein, mouseGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsReceptors, Gastrointestinal HormoneRecombinant Fusion ProteinsSemaglutideTirzepatideantidiabetic drugdrug developmentGIPGLP‐1 analogueweight control

Identifiers

PMID42410323
PMCPMC13448884

What OpenQuestion holds

Texttitle and abstract
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.