news-date">08.07.2022
A large Danish-American study suggests that taking metformin — a common drug used to treat Diabetes – before conception might increase the risk of birth defects.
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Metformin, a drug that has been used for decades, may increase the risk of birth defects in the offspring of men who took it during sperm development, according to a large Danish study. According to the study, published in the Annals of Internal Medicine, sons of these men were more likely to have abnormalities in their reproductive organs than unexposed babies. The genital defects such as hypospadias, when the urethra does not emerge from the tip of the penis, were relatively uncommon, occurring in 0.9% of all babies whose biological fathers had taken metformin in the 3 months prior to conception (compared to 0.24% of unexposed babies).
Millions of people around the world are taking metformin, so even low rates might be significant
Epidemiologists fear the findings are important given the tens of millions of people around the world who are prescribed metformin, mostly for type 2 diabetes. There overweight is an increasing problem in many countries and consequently also diabetes, more and more young men are also dependent on this drug. Experts interviewed by Science cautioned that the paper’s findings are preliminary and observational, and have yet to be confirmed. Factors other than metformin may have influenced the results. The scientists warned men with diabetes not to stop metformin abruptly before attempting to father a child with their wives.
“Metformin is a safe drug, it’s cheap and it does what it needs to do” by controlling blood sugar levels,” said the study’s first author, Assistant Professor Maarten Wensink, an epidemiologist and biostatistician at the University of Southern Denmark. Any change in medication “is a complex decision to make [ein Paar] should meet with their doctors,” he stressed.
The drug has been used since the 1950s, but this is the first major study to analyze any paternal-mediated effects on human birth defects. Although metformin use is geared toward older people, the rise in diabetes means more men are taking the drug into their reproductive years.
Period 90 days before conception seems to be important
Researchers analyzed records of more than 1.1 million babies born in Denmark between 1997 and 2016, using the country’s extensive medical registries to obtain data on births, fathers’ metformin prescriptions and birth defects, and possible associations to investigate. In the 1,451 offspring of men who filled metformin prescriptions in the 90 days before conception, the period when sperm are formed, the team found a 5.2% rate of birth defects, compared with 3.3% in unexposed babies. This translates to a 1.4 times greater likelihood of having at least one birth defect, including genital, digestive, urinary and urinary defects heart defect.
The numbers were small overall — 13 metformin-exposed boys were born with genital defects. But following the researchers adjusted for factors like parental age and mother’s smoking status, they found a 3.39-fold increase in the odds of having a genital defect. “The rate itself was surprisingly high,” says Wensink.
Researchers found no effects on the offspring of men who took the drug earlier in life or in the year before or following the 90-day sperm production window.
Preliminary results to be confirmed – other factors may play a role
However, the researchers concede that men with diabetes who took metformin and those who didn’t may have differed in other factors such as being overweight or how well their disease was controlled — data the experts didn’t have access to .
Scientists are also not sure how the drug affects sperm. Studies in fish and mice suggest that metformin may interfere with the development of male reproductive organs, and one small study found that metformin lowered serum testosterone levels in men.
Conclusions cannot yet be drawn and further research on this topic will be required.
Sources: Science, Annals of Internal Medicine
