ArticleAnnals of internal medicine2022
Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring : A Nationwide Cohort Study.
Article in Annals of internal medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Paternal use of metformin and risk of major congenital malformations: A meta-analysis of 4 studies.British journal of clinical pharmacology · 2026Pooled it
- Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials.BMC medicine · 2022Pooled it
- Paternal preconceptional metformin exposure induces metabolic dysregulation in offspring.Cell discovery · 2026Article
- The influence of paternal preconception health on birth defects and head circumference: A scoping review.PLOS global public health · 2026Article
- Article
- Effect of metformin on free testosterone level in male diabetic patients: A comparative study.Medicine · 2025 · on this mapObservational
- 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
- Safety concerns of paternal drug exposure on fertility, pregnancy and offspring: An analysis based on the FDA adverse event reporting system.Andrology · 2025Article
- Paternal Preconception Metformin Use and Offspring Risk of Congenital Malformations.JAMA network open · 2025Article
- A narrative review of metformin in pregnancy: Navigating benefit and uncertainty.Diabetes, obesity & metabolism · 2025Review
- Article
- Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study.BMJ (Clinical research ed.) · 2024Article
- Patterns of paternal medication dispensation around the time of conception.Paediatric and perinatal epidemiology · 2024Article
- Metformin use in pregnancy: What about long-term effects in offspring?Acta obstetricia et gynecologica Scandinavica · 2024Article
- Paternal Use of Metformin During the Sperm Development Period Preceding Conception and Risk for Major Congenital Malformations in Newborns.Annals of internal medicine · 2024Article
- Management of male obesity-related secondary hypogonadism: A clinical update.World journal of experimental medicine · 2024Review
- Reproductive chemical database: a curated database of chemicals that modulate protein targets regulating important reproductive biological processes.Cell & bioscience · 2024Article
- Future in the past: paternal reprogramming of offspring phenotype and the epigenetic mechanisms.Archives of toxicology · 2024Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundDiabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive system. Associations with birth defects in offspring are unknown.
objectiveTo evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes.
designNationwide prospective registry-based cohort study.
settingDenmark from 1997 to 2016.
participantsAll liveborn singletons from mothers without histories of diabetes or essential hypertension. MEASUREMENTS: Offspring were considered exposed if their father filled 1 or more prescriptions for a diabetes drug during the development of fertilizing sperm. Sex and frequencies of major birth defects were compared across drugs, times of exposure, and siblings.
resultsOf 1 116 779 offspring included, 3.3% had 1 or more major birth defects (reference). Insulin-exposed offspring ( LIMITATION: Information on underlying disease status was limited.
conclusionPreconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation. PRIMARY FUNDING SOURCE: National Institutes of Health.
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Registered trials
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.