Evidence mapPaperPMID 40887134Full record

ArticleBMJ open diabetes research & care2025

Association of metformin treatment with changes in metal dynamics in individuals with type 2 diabetes.

Natsu Otowa-Suematsu, Kazuhiko Sakaguchi, Tomoko Yamada, Marika Nishisaka, Yasuko Morita, Hayato Fukumitsu, Yukari Katsura, Yuko Okada, Yushi Hirota, Kenji Sugawara and 1 more

Abstract read
In one paragraph

Article in BMJ open diabetes research & care, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Copper dysregulation in cardiometabolic disease: copper deficiency versus cuproptosis.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. Article
  3. 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

11 authors.

Natsu Otowa-SuematsuDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.ORCID http://orcid.org/0000-0003-4982-0336
Kazuhiko SakaguchiDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Tomoko YamadaDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Marika NishisakaDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Yasuko MoritaDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Hayato FukumitsuDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Yukari KatsuraDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Yuko OkadaKagayaki Diabetes and Endocrinology Clinic Sannomiya, Kobe, Japan.
Yushi HirotaDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Kenji SugawaraDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Wataru OgawaDivision of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan ogawa@med.kobe-u.ac.jp.ORCID http://orcid.org/0000-0002-0432-4366

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe metal-chelating activity of metformin, which has long been known but of unclear clinical relevance, has recently been implicated in the pleiotropic effects, including antitumorigenic and anti-inflammatory actions, of the drug. However, whether metformin actually influences metal dynamics in humans has remained unknown. We here investigate whether metformin influences serum metal levels in individuals with type 2 diabetes. RESEARCH DESIGN AND

methodsIn this cross-sectional study, individuals with type 2 diabetes treated or not treated with metformin for at least 6 months were recruited. The primary outcome was the difference in serum copper concentration between metformin users and non-users. Secondary outcomes included differences in serum levels of iron, zinc, and vitamin B

resultsA total of 189 individuals (93 metformin users and 96 non-users) were analyzed. Metformin users showed significantly lower serum copper (16.0 vs 17.8 µmol/L, p<0.001) and iron levels (16.3 vs 17.3 µmol/L, p=0.02) and higher zinc levels (13.3 vs 12.5 µmol/L, p=0.01) compared with non-users. Copper-related and iron-related parameters for metformin users were consistent with latent deficiencies of these metals. Serum homocysteine levels (12.2 vs 11.2 µmol/L, p=0.03) were significantly higher, whereas vitamin B

conclusionsMetformin use was associated with reduced serum levels of copper and iron, as well as with increased serum zinc levels. These changes in metal dynamics may be related to the pharmacological effects of this widely administered drug.

Indexed as

BiomarkersCopperDiabetes Mellitus, Type 2Hypoglycemic AgentsIronMetalsMetforminAgedCross-Sectional StudiesFemaleFollow-Up StudiesHumansMaleMiddle AgedPrognosisVitamin B 12BiomarkersCopperHypoglycemic AgentsIronMetalsMetforminVitamin B 12ZincCopperDiabetes Mellitus, Type 2Metformin

Identifiers

PMID40887134
PMCPMC12406903

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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.