Evidence map›Paper›PMID 39908200›Full record

ArticleThe Journal of clinical endocrinology and metabolism2025

Semaglutide Reprograms Macrophages via the GLP-1R/PPARG/ACSL1 Pathway to Suppress Papillary Thyroid Carcinoma Growth.

Longlong Wang, Lele Zhang, Runsheng Ma, Yifei Zhang, Qungang Chang, Detao Yin

Abstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Exposure to GLP-1RA and Risk of Structural Progression in Differentiated Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2026
    Observational
  4. Review
  5. Review
  6. Review
  7. Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. 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

6 authors.

Longlong WangDepartment of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou 450052, China.
Lele ZhangDepartment of Liver Transplantation, the First Affiliated Hospital of Zhengzhou University of Henan Province, Zhengzhou 450052, China.
Runsheng MaDepartment of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou 450052, China.
Yifei ZhangDepartment of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou 450052, China.
Qungang ChangDepartment of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou 450052, China.
Detao YinDepartment of Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University, Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou 450052, China.ORCID 0000-0002-4349-6857

Funding

Key Medical Science and Technology Project of Henan Province 2023HYTP031Key Medical Science and Technology Project of Henan Province LHGJ20210322Key Medical Science and Technology Project of Henan Province SBGJ202101014
6 · The paper itself

Abstract

contextThe use of glucagon-like peptide-1 receptor (GLP-1R) agonists such as semaglutide, a novel class of antidiabetic medications, has raised concerns about potential adverse effects, particularly a possible association with thyroid cancer (TC).

objectiveThis study aims to evaluate whether semaglutide influences the progression of TC by modulating tumor-associated macrophages (TAMs).

methodsSemaglutide was administered to human papillary thyroid carcinoma (PTC) xenograft mouse models, coculture systems consisting of human THP-1 macrophage cells and PTC cells, and primary murine peritoneal macrophages. Assessments included tumor size, M1/M2 macrophage ratio, PTC cell proliferation, and polarization marker expression.

resultsSemaglutide did not significantly impact the proliferation of PTC cells but reduced tumor size and inhibited the proliferation of PTC cells in coculture systems. It increased M1 and decreased M2 macrophages, reprogramming polarization by downregulating PPARG expression. Cotreatment with semaglutide and a PPARG agonist in the coculture system confirmed the upregulation of downstream genes RSAD2, ACSL1, and PLA2G7. Silencing ACSL1 inhibited lipid accumulation in THP-1 cells and promoted polarization toward the M2 macrophage phenotype.

conclusionSemaglutide modulates macrophage lipid metabolism through the GLP-1R/PPARG/ACSL1 signaling pathway. This modulation promotes the conversion of TAMs to the M1 macrophage phenotype, enhancing their anticancer activity. These findings suggest that semaglutide may improve therapeutic strategies, reduce unnecessary thyroid nodule screenings, and broaden its clinical applications.

Indexed as

Glucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesMacrophagesThyroid Cancer, PapillaryThyroid NeoplasmsTumor-Associated MacrophagesAnimalsCell Line, TumorCell ProliferationFemaleGlucagon-Like Peptide 1HumansMiceSemaglutideSignal TransductionXenograft Model Antitumor AssaysGLP1R protein, humanGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesSemaglutideGLP-1R signalingmacrophage polarizationpapillary thyroid carcinomasemaglutidetumor-associated macrophages

Identifiers

PMID39908200
PMCPMC12448615

What Socratic 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 Socratic graph.