A nationwide study in Denmark has revealed that men with diabetes who are treated with metformin have an increased risk of having children with birth defects compared with non-diabetic men, or men treated with insulin.

Diabetes is known to impact male fertility and type 2 diabetes in particular is becoming more and more common in men of reproductive age. To assess this in more detail, Maarten Wensink, a clinical researcher based at the University of Southern Denmark Faculty of Health Sciences, and colleagues investigated whether the type of pharmacological treatment for diabetes impacts rates of birth defects in children of men with the condition.

The study, published in the Annals of Internal Medicine, included all single births born to mothers without diabetes or hypertension in Denmark between 1997 and 2016. In total, 1,116,779 births were included, 3.3% of which had at least one major birth defect.

Overall, 5298 fathers were prescribed insulin and their offspring appeared to have no increased risk for birth defects. Offspring of fathers who took metformin during the time the fertilizing sperm were developing (1451 births) had a 40% increase in relative risk for birth defects compared with insulin exposed offspring. However, there was no increased risk in the offspring of men who had taken metformin in the year before conceiving or after conceiving.

Of the birth defects observed following exposure to metformin, most were genital birth defects in boys and the overall number of male offspring in this group was lower than average at 49% (versus 51%).

The researchers also assessed exposure to sulfonylureas, another type 2 diabetes drug. While there did appear to be a small increase in relative risk for birth defects compared with insulin exposed offspring, it was not significant due to only 647 offspring being exposed to these drugs.

While the study is very interesting and raises possible concerns about the treatment of men with metformin while trying to conceive, the authors say more information and research replication is needed before conclusive medical recommendations can be made.

“One factor missing from the study is how well these men were regulating their diabetes and we already know that the disease itself can damage sperm quality,” said Sheena Lewis, Honorary Professor of Reproductive Medicine, Queen’s University Belfast, in a press statement.

“As couples wait until being older before starting families, their chances of being on medication for other chronic illnesses increases. The take home message is that men who are trying to have children should discuss all other medications with their family doctors to ensure these have no known adverse effects on male fertility.”