The study, conducted outside Denmark, used national records to track more than 1 million births between 1997 and 2016 and compared the risk of major genetic abnormalities in babies based on the father’s exposure to diabetes drugs. The study observed only children born to women under 35 and men under 40. Babies born to women with diabetes were excluded. The researchers found that men were exposed to metformin if they completed a prescription for it three months before conception, that is, how long it takes for the fertilized sperm to fully mature. According to the study, the incidence of genetic abnormalities in infants born to men diagnosed with type 2 diabetes but not taking metformin was 3.1% (1,594 children), but the incidence was 4.6% (788) in children with paternal exposure to metformin in the pre-conception period. Genetic abnormalities, observed only in male infants, were the only genetic defect in the study found to be associated with a statistically significant increased risk after metformin use by the father. Men who took metformin before or after the three-month maturation period did not have an increased risk of having a baby with a genetic disorder. Likewise, the unprotected baby siblings were not affected. Because previous research has shown that diabetes can compromise sperm quality and impair male fertility, the researchers also compared the rates of genetic abnormalities in the babies of men who received insulin with those of those who received metformin to ensure that The diagnosis of diabetes itself was not a contributing factor. They found that insulin use was not associated with a change in the rate of genetic abnormalities. The researchers found no significant correlation between genetic abnormalities and the father’s exposure to diabetes drugs other than metformin. However, the authors note that they had no data on other aspects of diabetes, such as glycemic control or drug compliance, as they evaluated the data only on when prescriptions were met. In addition, infants who were maternally exposed to metformin also tended to have older and lower socioeconomic parents, which may play a role. In an article published alongside the study, Germain Buck Louis, a reproductive and perinatal epidemiologist at George Mason University who did not participate in the study, said there was evidence from previous studies that “altered testosterone levels may be an underlying mechanism.” which raises concerns about the antiandrogenic action of oral pharmacological agents for diabetes, including metformin “to explain these findings. Louis also noted that due to the limitations of this study, further research is needed to determine whether men taking metformin should be considered, especially given the high prevalence of diabetes that may require metformin use. There are currently no warnings from the US Food and Drug Administration against the use of metformin by men planning to have children. “Clinical guidance is needed to help couples planning a pregnancy weigh the risks and benefits of paternal metformin over other drugs,” Louis wrote.
