ArticleAnnals of internal medicine2024
Paternal Use of Metformin During the Sperm Development Period Preceding Conception and Risk for Major Congenital Malformations in Newborns.
Article in Annals of internal medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Paternal use of metformin and risk of major congenital malformations: A meta-analysis of 4 studies.British journal of clinical pharmacology · 2026Pooled it
- Antidiabetic agents and male fertility: unraveling the impact of glucose-lowering therapies on sperm quality in diabetic males-a narrative review.Translational andrology and urology · 2025Review
- Associations of maternal and paternal characteristics with cardiac malformations using real-world data and machine learning.Communications medicine · 2025Article
- Beyond Genes: Mechanistic and Epidemiological Insights into Paternal Environmental Influence on Offspring Health.Current environmental health reports · 2025Review
- Paternal Preconception Metformin Use and Offspring Risk of Congenital Malformations.JAMA network open · 2025Article
- Patterns of paternal medication dispensation around the time of conception.Paediatric and perinatal epidemiology · 2024Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundMetformin is the most used oral antidiabetic medication. Despite its established safety profile, it has known antiandrogenic and epigenetic modifying effects. This raised concerns about possible adverse developmental effects caused by genomic alterations related to paternal use of metformin during the spermatogenesis period preceding conception.
objectiveTo assess the potential adverse intergenerational effect of metformin by examining the association between paternal metformin use during spermatogenesis and major congenital malformations (MCMs) in newborns.
designNationally representative cohort study.
settingA large Israeli health fund.
participants383 851 live births linked to fathers and mothers that occurred in 1999 to 2020. MEASUREMENTS: MCMs and parental cardiometabolic conditions were ascertained using clinical diagnoses, medication dispensing information, and laboratory test results. The effect of metformin use on MCMs was estimated using general estimating equations, accounting for concurrent use of other antidiabetic medications and parental cardiometabolic morbidity.
resultsCompared with unexposed fathers, the prevalence of cardiometabolic morbidity was substantially higher among fathers who used metformin during spermatogenesis, and their spouses. Whereas the crude odds ratio (OR) for paternal metformin exposure in all formulations and MCMs was 1.28 (95% CI, 1.01 to 1.64), the adjusted OR was 1.00 (CI, 0.76 to 1.31). Within specific treatment regimens, the adjusted OR was 0.86 (CI, 0.60 to 1.23) for metformin in monotherapy and 1.36 (CI, 1.00 to 1.85) for metformin in polytherapy, a treatment that was more common in patients with more poorly controlled diabetes. LIMITATION: Laboratory test results for hemoglobin A
conclusionPaternal use of metformin in monotherapy does not increase the risk for MCMs. Association for metformin in polytherapy could potentially be explained by worse underlying parental cardiometabolic risk profile. PRIMARY FUNDING SOURCE: None.
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