Published in the Annals of Internal Medicine this week, the study analyzed the data of over one million babies born in Denmark over a 20-year period ending in 2016. They found that kids born to dads who took Metformin in a 90-day window before conception had a 5.2 percent chance of a birth defect, while kids born to dads who didn’t take the medication had a 3.3 percent chance of birth defects.
While that might not sound like much, that 1.9 percent increase is a 40 percent overall increase in birth defects associated with the drug — and a much larger increase when specifically talking about genital birth defects in boys. When adjusted for factors like parental age and maternal smoking, the odds of a baby having a genital birth defect was 3.39 times higher if a dad was taking the diabetes drug.
“The rate per se was surprisingly high,” the paper’s first author, Maarten Wensink, an epidemiologist and biostatistician at the University of Southern Denmark, told Science.
This is especially significant because Metformin is an extremely common drug that is only gaining in popularity and usage due to the steeply increasing rates of type 2 diabetes and obesity in the United States. About 86 million Americans filled a prescription for Metformin in 2019, up from 41 million in 2004. That’s 26 percent of our population.
“[Metformin] is widely used even by young men because of the obesity issue that we have. So that is potentially a huge source of exposure for the next generation,” says Germain Buck Louis, a reproductive and perinatal epidemiologist at George Mason University who wrote an editorial published alongside the study.
“When I saw the paper … I thought: ‘Yup, this is gonna go viral,’” he continues.
The genital birth defects include undescended testicles and urethral problems.
It’s important, though, to talk to your doctor before making any decisions about stopping the drug based on one study — Metformin is popular because it’s often the best option to keep diabetes patients healthy, and stopping the drug could have adverse effects.
“Metformin is a safe drug, it’s cheap, and it does what it needs to do,” says Wensink. Taking the drug “is a complex decision that [a couple] should take together with their physicians.”
The study did not find a link between birth defects and other types of diabetes drugs. It also saw no increase in birth defects in the children conceived outside the 90-day window of Metformin usage, which implies that the drug may affect a man’s sperm.
Louis agreed with the study’s author. "Clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications," he writes.
Researchers were also quick to note the limits of this study. While it was large, it only focused on babies in one part of the world — and more studies need to be done. It also didn’t completely rule out other factors, like socioeconomic status or how compliant men were when taking the medication. It will definitely be important to investigate this link further, though, especially as more and more millions of people begin taking this drug.