A large Danish-American study suggests that taking metformin, a common drug used to treat diabetes, before conception could increase the risk of birth defects.
According to a large Danish study, 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 the study, published in the Annals of Internal Medicine, the children of these men were more likely to have abnormalities in their reproductive organs than unexposed children. Genital defects such as hypospadias, when the urethra does not protrude from the tip of the penis, were relatively rare and occurred in 0.9% of all children whose biological fathers had taken metformin in the 3 months prior to conception ( compared to 0.24% of unexposed children).
Millions of people around the world are taking metformin, so even low rates could be significant
Epidemiologists fear the findings are important given the tens of millions of people around the world who are prescribed metformin, primarily for type 2 diabetes. As obesity is a growing problem in many countries, and as a result diabetes is also a growing problem. , more and more young men are dependent on this drug. Experts interviewed by Science warned that the paper’s findings are preliminary and observational and have yet to be confirmed. Factors other than metformin may have influenced the results. Scientists have warned men with diabetes not to abruptly stop metformin before attempting to father a child with their wives.
“Metformin is a safe drug, it’s cheap, and it does what it’s supposed to do by” controlling blood sugar levels, “said the study’s first author, assistant professor Maarten Wensink, epidemiologist and biostatistician at the University of Southern Denmark. Any change in therapy “is a complex decision to make [ein Paar] they should meet their doctors, ”he stressed.
The drug has been used since the 1950s, but this is the first major study to investigate any paternity-mediated effects on human birth defects. Although the use of metformin is aimed at older people, the increase in diabetes means that more men take the drug in their reproductive years.
The 90-day period before conception appears to be important
The researchers analyzed the records of more than 1.1 million babies born in Denmark between 1997 and 2016, using the country’s extensive medical registers to obtain data on births, paternal prescriptions for metformin, birth defects and possible associations on which to investigate. In the 1,451 children of men who filled their prescriptions for metformin in the 90 days before conception, the period in which sperm are formed, the team found a 5.2% rate of birth defects, compared with 3.3%. in unexposed children. This is 1.4 times more likely to have at least one birth defect, including genital, digestive, urinary, and heart defects.
The numbers were small overall: 13 boys exposed to metformin were born with genital defects. But after researchers adjusted for factors such as the age of the parents and the smoking status of the mother, they found a 3.39-fold increase in the odds of having a genital defect. “The rate itself was surprisingly high,” says Wensink.
The researchers found no effects on the offspring of men who took the drug earlier in life or in the year before or after the 90-day sperm production window.
Preliminary results to be confirmed: other factors may play a role
However, the researchers admit that men with diabetes who took metformin and those who did not may differ in other factors such as being overweight or how their disease was controlled, data that experts did not have access to.
Scientists also aren’t 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.
It is not yet possible to draw any conclusions and more research on this topic will be needed.
Quellen: Science, Annals of Internal Medicine