Evidence map›Paper›PMID 41937475›Full record

SynthesisBritish journal of clinical pharmacology2026

Paternal use of metformin and risk of major congenital malformations: A meta-analysis of 4 studies.

Per Damkier, Marleen M H J van Gelder, Krista F Huybrechts, Lin-Chieh Meng, Sonia Hernandez-Diaz, Jan Nielsen, Bente M Nørgård, Hedvig Nordeng

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in British journal of clinical pharmacology, 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.

Per DamkierDepartment of Clinical Pharmacology, Odense University Hospital, Odense, Denmark.ORCID https://orcid.org/0000-0003-0591-7187
Marleen M H J van GelderPharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo, Oslo, Norway.ORCID https://orcid.org/0000-0003-4853-4434
Krista F HuybrechtsDepartment of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Lin-Chieh MengGraduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Sonia Hernandez-DiazDepartment of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Jan NielsenCenter for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.
Bente M NørgårdCenter for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.ORCID https://orcid.org/0000-0002-9514-3033
Hedvig NordengPharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, University of Oslo, Oslo, Norway.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metformin is the first-line drug for the treatment of Type 2 diabetes. In 2022, a Danish registry-based study reported a 40% increased risk of major congenital malformations following paternal exposure during spermatogenesis. This raised widespread concern about the use of metformin in males of reproductive age. Three subsequent studies were unable to replicate this finding. We performed a meta-analysis of four observational studies with data from five countries covering more than 11 000 live-born children whose fathers used metformin during spermatogenesis. The pooled risk ratio from an inverse variance-weighted random effects model was 1.03 (95% CI 0.88-1.21). We conclude that paternal exposure to metformin does not confer a meaningfully increased risk of major congenital malformations.

Indexed as

Abnormalities, Drug-InducedHypoglycemic AgentsMetforminPaternal ExposureDiabetes Mellitus, Type 2HumansMaleObservational Studies as TopicRisk FactorsSpermatogenesisHypoglycemic AgentsMetformincongenitalmalformationsmetforminpaternal use

Identifiers

PMID41937475
PMCPMC13206475

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY-NC-ND
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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.