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Background
Metformin is widely prescribed to manage type 2 diabetes, a condition that can affect men during their reproductive years. However, recent research from Denmark raised concerns about a potential link between paternal metformin use and an increased risk of congenital malformations, particularly genital defects in male infants. These findings sparked debate and concern among healthcare providers and potential fathers alike.
To address this issue, researchers from Norway and Taiwan conducted a comprehensive study aimed at evaluating whether paternal use of metformin is associated with an increased risk of congenital malformations.
The Study
The researchers used national birth registries and prescription databases from Norway and Taiwan to track the health outcomes of children born to fathers who took metformin during sperm development (three months before pregnancy). The study included data from 619,389 pregnancies in Norway (2010–2021) and 2,563,812 pregnancies in Taiwan (2004–2018).
In Norway, congenital malformations were found in 5% of the offspring of fathers who used metformin during the sperm development period, compared to 3.9% in children of fathers who did not use the drug. In Taiwan, 3.4% of children born to fathers on metformin had congenital malformations, compared to 3.1% for those whose fathers did not take the medication.
However, when the analysis was limited to fathers with type 2 diabetes, and adjustments were made for factors such as age and other health conditions, the study found no increased risk of congenital malformations in offspring of fathers using metformin. No specific organ malformations, including genital defects, were associated with metformin use.
Implications and Limitations
Although the findings offer significant reassurance to clinicians and families, the study’s authors caution that the results are observational and cannot establish direct causality. They also acknowledge potential limitations, such as inaccuracies in diagnostic data and the possibility of unmeasured factors influencing the results. Despite these caveats, the consistency of the findings after further analysis, accounting for genetic and family factors, suggests that the results hold up under scrutiny.
Expert Commentary
In a linked editorial, researchers from Australia addressed the discrepancies between this study and the earlier Danish findings. They suggest that differences in data quality and study methods may explain the conflicting results. Additionally, the absence of a biological mechanism linking metformin use in fathers to fetal malformations supports the conclusion that the medication is safe for men planning to conceive.
While the Danish study raised important questions, these new findings offer some reassurance to both healthcare professionals and fathers-to-be. The authors of the editorial call for further confirmatory studies but conclude that metformin can be considered a safe option for men with type 2 diabetes who are planning to start a family.
This research provides a critical update for clinicians managing type 2 diabetes in men, offering confidence that metformin remains a suitable treatment option without increasing the risk of congenital malformations in their children.
Source:
Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study. The BMJ (2024). DOI: 10.1136/bmj-2024-080127.
