Evidence map›Paper›PMID 41522742›Full record

ArticleJournal of gastrointestinal oncology2025

Metformin reshapes the tumor microenvironment and enhances prognosis in invasive pancreatic ductal adenocarcinoma with diabetes mellitus.

Rei Takahashi, Akira Saito, Hideyo Miyato, Yuki Kimura, Yuichi Aoki, Masanobu Taguchi, Kazue Morishima, Hideyuki Ohzawa, Kazuhiro Endo, Hideki Sasanuma and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of gastrointestinal oncology, 2025. 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

17 authors.

Rei TakahashiDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Akira SaitoDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Hideyo MiyatoDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Yuki KimuraDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Yuichi AokiDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Masanobu TaguchiDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Kazue MorishimaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Hideyuki OhzawaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Kazuhiro EndoDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Hideki SasanumaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Hironori YamaguchiDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Hiroshi KawahiraDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Hisanaga HorieDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Yoshinori HosoyaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Toshiki MimuraDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Joji KitayamaDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Naohiro SataDivision of Gastroenterological, General and Transplant Surgery, Department of Surgery, Jichi Medical University, Shimotsuke, Tochigi, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with diabetes mellitus (DM), and their prognosis remains particularly poor. Metformin, a widely used antidiabetic agent, has demonstrated anti-tumor effects through multiple mechanisms and has been associated with improved outcomes in various malignancies. In this study, we investigated retrospectively survival outcomes and intra-tumoral infiltration patterns of various immune cells in diabetic patients who underwent curative resection of PDAC, comparing those who received metformin with those who did not. Methods: A total of 65 diabetic patients who underwent curative resection for invasive PDAC were retrospectively analyzed. Among them, 17 patients received metformin, while 48 did not. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups. Following propensity score matching, tumor-infiltrating CD3(+) and CD8(+) T cells were assessed by immunohistochemistry (IHC), and their densities were compared between metformin users and non-users. Results: Patients in the metformin group showed significantly prolonged RFS [hazard ratio (HR) =0.42, P=0.03] and OS (HR =0.421, P=0.03) compared to those in the non-metformin group. Multivariate analysis identified metformin use as an independent prognostic factor for both RFS (HR =0.40, P=0.02) and OS (HR =0.21, P=0.02). The survival benefit of metformin was particularly evident in patients who underwent upfront surgery, whereas not significant in those who received neoadjuvant therapy. Immunohistochemical analysis revealed a significantly higher density of CD8(+) T cells (650.7 Conclusions: Metformin may enhance the infiltration of cytotoxic CD8(+) T cells into the tumor microenvironment and improve the prognosis of diabetic patients with PDAC, particularly in those undergoing upfront surgical resection.

Indexed as

diabetes mellitus (DM)metforminPancreatic ductal adenocarcinoma (PDAC)

Identifiers

PMID41522742
PMCPMC12780566

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.