For This Popular Diabetes Drug, a 'Surprisingly High' Risk

One of the most widely prescribed diabetes drugs has been linked to an increased risk of birth defects in the offspring of men who filled a prescription for it shortly before conception, according to new research. "When I saw the paper ... I thought: 'Yup, this is gonna go viral,'" Germaine Buck Louis, a reproductive epidemiologist at George Mason University who authored an editorial accompaniment to the report, tells Science. A first-line treatment for Type 2 diabetes, "[metformin] is widely used even by young men because of the obesity issue that we have," Louis notes. "So that is potentially a huge source of exposure for the next generation."

There were 86 million prescriptions for metformin, used to treat high blood-sugar levels, written in the US in 2019. As of 2015, some 768,000 prescriptions went to patients ages 18 to 49. That presents a concern, as the large study analyzing 1.1 million births in Denmark, published this week in the Annals of Internal Medicine, found babies born to men who filled a prescription for metformin in the 90 days before conception, when sperm was being made, were 1.4 times more likely to suffer a major birth defect than other babies, per Reuters. They had a 5.2% rate of birth defects, compared to 3.3% among unexposed infants. More significantly, 0.9%—13 boys—suffered rare genital defects, compared to 0.24% of unexposed babies.

The risk of genital defects "was surprisingly high," University of Southern Denmark epidemiologist Maarten Wensink, the lead author, tells Science. Researchers didn't find a similar risk in the offspring of men who filled a prescription for metformin—recently found to reduce serum testosterone levels—outside of the 90-day period before conception, or in the offspring of diabetic men who took insulin. But they note their data on metformin use is lacking, and "poorly controlled diabetes can reduce sperm quality." Men are cautioned not to stop taking the drug abruptly. "Clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use," writes Louis, per Live Science. (More birth defects stories.)