Re-evaluating paternal metformin use

In recent years, concerns have emerged regarding the potential impact of paternal use of metformin, a common diabetes medication, on the risk of birth defects in offspring.

A provocative Danish study published in 2022 in the Annals of Internal Medicine suggested that men who took metformin shortly before conception had an increased risk of fathering children with birth defects. This study hypothesised that metformin could adversely affect spermatogenesis, a mechanism observed in some animal studies.

A new study, published in the Annals of Internal Medicine, has now investigated this issue in a different population. Researchers analysed data from 1,730 fathers with diabetes in an Israeli health system database who were on metformin during the 90 days before conception. Their findings provide a more nuanced perspective on the potential risks associated with metformin use by prospective fathers.

The study adjusted for various potential confounders, including demographic, cardiometabolic, and maternal factors. The results indicated that metformin monotherapy was not linked to an increased risk of major congenital malformations when compared to the offspring of 380,000 control fathers who had no exposure to diabetes medications. However, the offspring of men who took metformin in combination with other diabetes medications showed a slightly higher incidence of malformations, though this finding was only of borderline statistical significance.

These findings offer some reassurance for men with diabetes who require metformin therapy but also underscore the importance of further research to fully understand the potential reproductive implications of diabetes medications.