October 16, 2024

expert reaction to study of metformin and birth defects

A study published in the BMJ looks at metformin use and the risks of birth defects in offspring. 

Dr Channa Jayasena, Consultant & Head of Andrology, Imperial College London, said:

“Metformin is one of the most important drugs in the world, by providing an affordable and effective way to lower sugar levels in millions of patients with type 2 diabetes around the world. A previous study suggested that men taking metformin might be at increased risk of fathering children with birth defects, but I always urge caution with such studies because they can scare people away from medications that they need, because of a potential but unproven risk. 

“The current study studied more than 3 million pregnancies, making it very large by current standards. Importantly, they found no increase in birth defects when men took metformin. This allows us to reassure men taking the drug that there is no consistent evidence suggesting that their children will be at increased risk of birth defects.”

Prof Allan Pacey, Professor of Andrology at the University of Manchester, said:

“This is a useful study that provides further clarity on the relationship between metformin use to control type 2 diabetes in fathers and birth defects in their sons. This has been of interest since the publication of a paper in 2022 by researchers using data from Denmark in which suggested there might be a link.

“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. The makes sense because there was never any plausible biological mechanism which might have led us to this conclusion.

“I think the reasons that this new paper finds no link, compared to the 2022 paper which did, is simply down to data quality. Both analyses were very well conducted, but in this paper using data from Norway and Taiwan, the authors were able to take into account many more confounding factors. This highlights the need for ongoing caution in the interpretation of observational studies like this and why they should always be repeated in many different populations before a firm conclusion is drawn.

“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.”

‘Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study’ by Lin-Chieh Meng et al. was published in The BMJ at 23:30 hours UK time on Wednesday 16 October 2024.

DOI: 10.1136/bmj-2024-080127

Declared interests

Allan Pacey: “Chairman of the advisory committee of the UK National External Quality Assurance Schemes in Reproductive Science, Emeritus Editor in Chief of Human Fertility, Trustee of the Progress Educational Trust (Charity Number: 1139856) and Patron of the Fertility Alliance (Charity Number:1206323) (all unpaid).”

Channa Jayasena: “No conflicts”