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Use of metformin in men and birth defects in offspring

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Use of metformin in men and birth defects in offspring

A study (n=1,116,779 offspring) found overall frequency of >=1 major defects & birth defects (BDs) in insulin-exposed offspring (n=5298) were as per reference BD frequency (BDF), however metformin-exposed offspring (n=1451) had elevated BDF particularly genital birth defects in boys (1)

  • in the study, adjusted odds ratio of birth defect was 1.40 [95% CI, 1.08 to 1.82]) in metformin-exposed offspring

  • accompanying editorial discusses birth defects as leading cause of infant mortality in many geographic regions and challenges of identifying emerging teratogens especially in the context of rapid changes in the health status of reproductive-aged populations such as the growing percentage of young adults who are overweight or obese

Patient advice based on the study (2):

  • poorly controlled diabetes can reduce sperm quality. However, the effects of diabetes medications on sperm quality are uncertain. Information is lacking about the risk for birth defects in babies born to fathers with diabetes. If birth defects were more common with some diabetes medications, birth outcomes could potentially be improved if men with diabetes switched to other diabetes medications when trying to father a child

  • study limitations:
    • there are newer drug classes used to treat type 2 diabetes that were not studied
    • study did not account for how well a father's diabetes was controlled during sperm development
    • researchers were unable to determine whether fathers taking insulin had type 1 or type 2 diabetes
    • metformin and sulfonylureas are only used to treat type 2 diabetes, so it is reasonable to assume that the fathers receiving these drugs had type 2 diabetes

  • concluding remarks:
    • "..Metformin taken during the period of sperm development seems to increase the risk for birth defects in babies fathered during this time. Further studies are needed to confirm and better understand this association. However, men with diabetes who are taking metformin should talk to their doctors about whether they should switch to another treatment when trying to conceive a child. Because diabetes control also affects sperm quality, discontinuing metformin treatment could also affect birth outcomes.."


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