Men taking metformin can be reassured that there is no link with birth defects, say researchers who reviewed data from more than three million pregnancies.

The study was done after Danish researchers reported a possible association in 2022 but for which there was ‘no plausible biological mechanism’.

Now a careful analysis of national birth registries and prescription databases from Norway and Taiwan has shown no increased risk of any congenital malformations among infants born to fathers who used metformin during the three months before pregnancy.

The researchers concluded in the BMJ that metformin is a suitable drug for managing blood sugar levels in men with type 2 diabetes who plan on having children

In 2022, the Danish study reported a link between metformin use by fathers-to-be and an increased risk of congenital malformations, particularly genital, in male infants.

The most recent analysis looked at 619,389 children in Norway with paternal data during the three months before pregnancy and 2,563,812 in Taiwan.

It showed that fathers of 2,075 (0.3%) children in Norway and 15,276 (0.6%) in Taiwan used metformin during the sperm development period.

In Norway, congenital malformations were found in 24,041 (3.9%) children of fathers who did not use metformin during the period of sperm development, compared with 104 (5%) from those who used the drug.

Similarly, in the larger Taiwan database, congenital malformations were found in 79,278 (3.1%) offspring of fathers who did not use metformin, compared with 512 (3.4%) offspring of fathers who used metformin.

A further analysis just looking at those fathers who had type 2 diabetes, and adjusting for age and related conditions, there was no increased risk of any congenital malformations associated with metformin use in either Norway or Taiwan.

No notable increases in risk were found for any specific organ malformations, including genital malformations, the researchers reported.

The findings were consistent after further analyses accounting for genetic and family factors, suggesting they are robust, the authors explained.

‘These results provide reassurance and can assist clinicians in making informed treatment decisions when selecting metformin in the treatment of type 2 diabetes mellitus among men who are planning a family,’ they concluded.

Professor Allan Pacey, professor of andrology at the University of Manchester, said the useful study had provided further clarity on the issue,

‘By using data from two different populations in Norway and Taiwan, the new paper has taken the analysis one step further and have concluded that no real link exists between a father’s metformin use and any birth defects in his sons.

‘This makes sense because there was never any plausible biological mechanism which might have led us to this conclusion.’

He added that the reason for the differing results between this and the Danish study was likely down to data quality and highlights the need for ongoing caution in the interpretation of observational studies.

‘At the time that the original Danish study was published in 2022, many of us expressed caution about how the findings might be interpreted and encouraged men who take metformin to control their diabetes to continue doing so, or at least discuss it with their doctor.

‘I hope that this new study provides further reassurance that metformin is a safe drug that can be used for the control of type 2 diabetes in men who wish to become fathers.’

This article first appeared on our sister site Pulse.