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5MinuteConsult Journal Club

Preconception Metformin Use in Men Increases Birth Defects


Ann Intern Med 2022 Apr; [e-pub]. (

Study Summary

Using a national database in Denmark, researchers compared paternal use of diabetes medication in the 3 months prior to conception and rate of birth defects over 20 years. Metformin may cause lower testosterone levels possibly influencing sperm quality.


Overall, 3.3% of the children had 1 or more birth defects. Insulin and sulfonylureas had no significant impact on the rate of birth defects, but men who had used metformin prior to conception showed increased odds (aOR=1.40; CI, 1.08-1.82). There was no increase in risk if metformin was used (and believed stopped) in the months before conception or started after conception. Among those on metformin during conception, genital birth defects in males were more common.


Metformin use by fathers in the 3 months prior to conception increased the risk of major birth defects, in particular genital abnormalities.


This study, while observational, is the best type of data one can ethically obtain. It implies we need to counsel young males on metformin that should they plan to have children, to stop it for at least 3 months… maybe 4-5 months before. Yes, this was a uniform society in Denmark, so we do not know if it will apply to the rest of the world. This will likely spur more case-control study in other parts of the world. Till then, recommend stopping metformin for those men considering having children.

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