September 25, 2022

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Metformin causes a 2.39-fold increased risk of genital defects in offspring



 

Metformin causes a 2.39-fold increased risk of genital defects in offspring if men taking it 3 months before his wife pregnancy.


There is such a “magic drug”, which is used by about 150 million people around the world. It has a variety of magical effects, but the drug price is not expensive – it is metformin.

 

Metformin is not only one of the most widely used oral hypoglycemic drugs, but also new research shows that it has more than 20 kinds of effects, including, combined with other drugs can reduce the incidence of cancer, reduce the risk of heart disease, help Weight control, anti-aging and anti-inflammatory… Previously, bioRxiv published a new study showing that metformin can even reduce the new coronavirus load in single cells!

 

 

Almost every month, “possible new effects” of metformin are discovered. If you don’t believe it, you can search for “metformin” on the Mays public account. Therefore, people in the medical community joked, “Metformin is no longer a medicine, but the key to open a new era of the universe.”

 

However, a recent study made the “magic medicine” miserable.

 

A large cohort study conducted by researchers from the University of Southern Denmark in Denmark and Stanford University in the United States found that metformin in men taking metformin during sperm development (3 months before conception) was associated with an increased risk of birth defects, especially in boys. genital defects. The study was published March 29 in the Annals of Internal Medicine.

 

Metformin causes a 2.39-fold increased risk of genital defects in offspring if men taking it 3 months before his wife pregnancy.

https://doi.org/10.7326/M21-4389

 

Previous studies have found that some diabetes drugs may damage sperm quality and affect male reproductive health. Therefore, in this study, the researchers compared whether men taking different hypoglycemic drugs, including insulin, metformin, and sulfonylureas during sperm development, had differences in the risk of birth defects in offspring.

 

The study included the postnatal development of 1,116,779 infants from Denmark from 1997-2016 whose mothers did not have diabetes or high blood pressure. Of these, 3.3% of newborns had at least one serious birth defect.

 

It takes about 3 months to develop from prospermia to fully mature sperm. During this period, offspring were considered to have been exposed to diabetes drugs if the father had taken at least one prescription drug. Ultimately, a total of 7029 infants in this study were exposed to diabetes medications, including 5298 with insulin, 1451 with metformin, and 647 with sulfonylureas.

 

Metformin causes a 2.39-fold increased risk of genital defects in offspring if men taking it 3 months before his wife pregnancy.

 

The data survey found that compared with the control group, the use of insulin by fathers to lower blood sugar did not increase the risk of neonatal birth defects (aOR=0.98, [95% CI, 0.85 to 1.14]) . However, offspring exposed to metformin had a higher rate of birth defects, with a 40% increased risk (aOR=1.40, [95% CI, 1.08 to 1.82]) .

 

Offspring exposed to sulfonylureas were associated with a 34% increased risk of birth defects (aOR=1.34, [95% CI, 0.94 to 1.92]) , although the researchers concluded that the risk of birth defects was increased by 34% in males taking sulfonylureas. The sample size is too small to get an accurate answer.

 

So the researchers turned their attention to metformin. Further studies showed that the risk of genital defects was significantly increased in neonates exposed to metformin, 3.39 times higher than in the control group (aOR=3.39, [95% CI, 1.82 to 6.30]) , all in boys .

In addition, the risk of chromosomal abnormalities, cardiac birth defects, and urinary organ defects increased by 116%, 58%, and 38%, respectively.

 

Metformin causes a 2.39-fold increased risk of genital defects in offspring if men taking it 3 months before his wife pregnancy.

 

However, studies have shown that the use of metformin by fathers before or after sperm development does not increase the risk of birth defects in babies. It also did not affect the risk of birth defects in other siblings who were not exposed to metformin.

 

Taken together, paternal use of metformin during sperm development was associated with a 40% increased risk of birth defects in newborns compared with other blood sugar-lowering drugs.

Among them, the genital defects of male infants were the most affected, and the incidence was 3.39 times that of the control group.

 

This study is a reminder for expectant dads with diabetes. The “magic drug” metformin is also a double-edged sword. During pregnancy, you should discuss with your doctor whether to replace the diabetes treatment plan, and weigh the pros and cons of replacing metformin with other drugs and lifestyle adjustments.

 

Of course, the researchers stress that the paper also has certain flaws. Previous studies have shown that diabetes also affects sperm quality, but this study did not take into account whether the father’s diabetes was well controlled during sperm development.

At the same time, more new drugs for the treatment of diabetes have not been included, and more in-depth research is needed.

 

The so-called “drug is a three-point poison” and “a once-in-a-century anti-sugar drug” metformin also has both positive and negative sides, and it should be used with caution.

 

 

 

 

 

 

References
[1]Wensink MJ, Lu Y, Tian L, Shaw GM, Rizzi S, Jensen TK, Mathiesen ER, Skakkebæk NE, Lindahl-Jacobsen R, Eisenberg ML. Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring : A Nationwide Cohort Study. Ann Intern Med. 2022 Mar 29. doi: 10.7326/M21-4389. Epub ahead of print. PMID: 35344380.

Metformin causes a 2.39-fold increased risk of genital defects in offspring if men taking it 3 months before his wife pregnancy.

(source:internet, reference only)


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