A new study published in the Annals of Internal Medicine has uncovered an alarming intergenerational impact of the common diabetes drug metformin. Researchers found that metformin use in men around the time of conception significantly increases the risk of genital birth defects in resulting male offspring.
The large-scale study analysed over 1 million births in Denmark between 1997-2016. Fathers who filled a metformin prescription in the three months prior to conception were considered to have exposed their sons during sperm development. Shockingly, these boys were more likely to be born with genital birth defects compared to the general population.
Lead researcher Dr. Michael Eisenberg, Professor of Urology at Stanford University, calls the magnitude of risk “sobering” and comparable to well-known maternal factors like advanced maternal age. Yet historically we know little about how paternal health impacts children compared to mothers. Eisenberg explains, “it makes sense that there could be some effects that travel through paternal pathways as well.”
Unraveling the Mystery of Paternal Impacts
The study controlled for diabetes itself, meaning the birth defects resulted from metformin specifically, not just having diabetes. Eisenberg elaborates, “It wasn’t just taking metformin at any time in a man’s life; it really has to do with taking it in that window when the sperm that is going to become the child is being developed.”
Moreover, no similar impacts occurred with other common diabetes medications like insulin and sulfonylureas. This further implicates metformin as the culprit behind increased genital birth defects.
Researchers also compared exposed babies to their unexposed siblings and found no increased birth defect rates. This means the issue did not result from factors affecting individual fathers. Altogether the meticulous study design homes in on metformin itself causing reproduction issues in men that later harm their sons.
Eisenberg notes metformin is already known to affect male reproductive health in mice. For instance, pregnant mice given the drug bear sons with smaller testes. However the means by which metformin travels intergenerationally remains uncertain. The decreased ratio of male to female babies hints that harm may be so severe in some cases it prevents implantation or embryonic development of males.
Should Men Quit Metformin Before Conceiving?
Metformin prescriptions are skyrocketing as type 2 diabetes continues unchecked. Eisenberg maintains it is premature to condemn metformin outright given the limitations of a single study. Further validation across diverse populations can clarify metformin’s safety profile for men trying to conceive. Nonetheless, the startling findings merit consideration.
Eisenberg concludes, “When we think about reproduction, we still mostly think about maternal factors, so this study brings further awareness that paternal factors can make a difference. Don’t forget the father.” At minimum, it spotlights how men’s health around conception impacts future children, contrary to traditional mindsets. Until further research brings clarity, men with diabetes should discuss medications with their doctor if planning for children. Together they can weigh alternatives to mitigate potential risks to both short and long-term reproductive health for men and babies alike.
Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring
