No Major Birth Defects Linked to Paternal Metformin Use: Study

A study published in the Annals of Internal Medicine found that paternal use of metformin monotherapy was not associated with major congenital malformations (MCMs) in newborns. Associations between metformin in polytherapy and birth defects could potentially be explained by the worse underlying parental cardiometabolic risk profile of those taking multiple diabetes medications.

Paternal use of metformin involves men taking the medication, often to manage type 2 diabetes, during the period of sperm production before conception. Metformin helps regulate blood sugar levels by reducing glucose production in the liver, improving insulin sensitivity, and decreasing sugar absorption in the intestines. While metformin is primarily used to treat diabetes, it has also been studied for other potential health benefits.

In the study, researchers analyzed data from 400,000 live births between 1999 and 2020 to see if using metformin during the time sperm is produced before conception could cause problems in the next generation. They checked for major birth defects and parental heart and metabolic conditions by reviewing medical diagnoses, medication records, and lab test results.

The results indicated that metformin use by fathers was initially linked to a higher risk of major congenital malformations (MCM) in children (6.2% compared to 4.7% with no diabetic medication).

However, this association disappeared after adjusting for paternal cardiovascular and metabolic conditions and excluding children born to mothers with diabetes or hyperglycemia.

Fathers on metformin or other diabetic medications tended to be older, had cardiovascular and metabolic issues, were more likely to smoke, and had fertility problems. Similarly, when fathers used metformin, mothers were more likely to have cardiovascular co-morbidities and fertility issues.

“These findings underscore the importance of considering paternal health in the context of reproductive planning and prenatal care. Metformin is a safe and effective treatment option for type 2 diabetes for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester. As such, it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy for those trying to conceive,” said the authors.

Reference: Sarah Martins da Silva. Paternal and Maternal Metformin Use and the Risk for Major Congenital Malformations. Ann Intern Med. [Epub 18 June 2024]. doi:10.7326/M24-0883