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Metformin Prescriptions Linked to Sons’ Birth Defects

A new cohort study finds that boys whose fathers took the type 2 diabetes drug metformin three months before their conception were more likely to have a birth defect.

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Dan Robitzski

Dan is a Staff Writer and Editor at The Scientist. He typically works on the news desk and joined the team in 2021. He has a background in neuroscience and earned his master's in science journalism at New York University.

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Mar 29, 2022

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Men who took the type 2 diabetes drug metformin three months before conceiving their children seem to have an increased risk of having sons with birth defects, new research finds.

The study, a retroactive analysis of Denmark’s federal registry of healthcare data that was published Tuesday (March 29) in Annals of Internal Medicine, found a significantly increased risk of genital birth defects among boys whose fathers had filled a prescription for metformin—commonly branded as Glucophage, Riomet, and Glumetza—about three months prior to conception, roughly the duration of time it takes for sperm to mature. A correlation between birth defects and paternal metformin prescriptions was not seen in girls, according to the study.

“This could be an extra reason to put more priority on paternal health,” study coauthor Maarten Wensink, a public health expert at the University of Southern Denmark,” tells Reuters.

See “Diabetes Drug Grows Neurons

The study looked at medical records of children born between 1997 and 2016 whose fathers likely took metformin, insulin, or another diabetes medication (the healthcare registry has information on prescription records but doesn’t verify whether patients actually ingested the prescribed drugs). Records were only included if the mother was not prescribed any diabetes medication or diagnosed with the disease.

Of the roughly 1.1 million children whose records were analyzed, 3.3 percent had at least one major birth defect, according to the study. That number was notably higher—4.6 percent—among sons whose fathers were prescribed metformin three months prior to conception, CNN notes.

The trend was not found among those who took other diabetes medications. For example, only 3.1 percent of children whose fathers were diagnosed with type 2 diabetes but weren’t prescribed metformin had birth defects. Similarly, children who were conceived a year before the prescriptions were filled or fewer than three months after had baseline levels of birth defects, according to the study. The same was true even if they were the sibling of a child with a metformin-correlated birth defect, supporting the notion that the birth defects are linked to the medication’s acute impacts on sperm.

See “Metformin Users Have Different Gut Bugs

Germain Buck Louis, a George Mason University epidemiologist who wasn’t involved in the work, suggests in an accompanying editorial also published Tuesday in Annals of Internal Medicine that the birth defects may stem from the drug’s ability to reduce testosterone levels, but further research into the mechanism of the observed effect is necessary.

The US Food and Drug Administration doesn’t currently warn men planning on having children against taking metformin, according to CNN. But Wensink tells Reuters that perhaps men ought to switch diabetes drugs—with input from their doctors—before trying to conceive.

Imperial College London head of andrology Channa Jayasena cautions against altering clinical protocols immediately. “Men with diabetes should not be dissuaded from taking metformin, but this is worth looking at more closely,” Jayasena, who didn’t work on the study, tells Reuters, adding that the research is “thought-provoking but inconclusive.”