Metformin is a first-line drug in the treatment of type 2 diabetes.
The research, which was done out of Denmark, used national registries to follow over 1 million births between 1997 and 2016 and compared the risk of major birth defects in babies based on paternal exposures to diabetes medications. The study observed only children who were born to women under 35 and men under 40. Babies born to women with diabetes were excluded.
The researchers considered men exposed to metformin if they filled a prescription for it in the three months before conception, which is how long it takes the fertilizing sperm to fully mature.
According to the study, the frequency of birth defects in babies born to men who had a type 2 diabetes diagnosis but who were not taking metformin was 3.1% (1,594 children), but the frequency was 4.6% (788) in children with paternal exposure to metformin during the preconception period.
Genital birth defects, seen only in male babies, was the only birth defect in the study that was found to be associated with a statistically significant increased risk after paternal metformin use.
Men who took metformin before or after the three-month maturation period did not have an increased risk of having a baby with birth defects. Similarly, the babies’ unexposed siblings were not affected.
The researchers did not find any significant association between birth defects and paternal exposure to diabetes medication other than metformin.
However, the authors note that they did not have data on other aspects of diabetes, such as glycemic control or medication compliance, as they assessed data only on when prescriptions were filled. In addition, babies who had paternal metformin exposure also tended to have parents who were older and of a lower socioeconomic status, which may play a role.
Louis also noted that due to the limitations of this study, further research is needed to find out whether men taking metformin should make any considerations, especially given the high prevalence of diabetes that may require metformin use.
There are currently no US Food and Drug Administration warnings against the use of metformin by men planning to have children.
“Clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications,” Louis wrote.